Daniel A. Jones

Successful Recanalization of Chronic Total Occlusions Is Associated With Improved Long-Term Survival

OBJECTIVES This study investigated the impact of procedural success on mortality following chronic total occlusion (CTO) percutaneous coronary intervention (PCI) in a large cohort of patients in the drug-eluting stent era. BACKGROUND Despite advances in expertise and technologies, many patients with CTO are not offered PCI. METHODS A total of 6,996 patients underwent elective PCI for stable angina at a single center (2003 to 2010), 836 (11.9%) for CTO. All-cause mortality was obtained to 5 years (median: 3.8 years; interquartile range: 2.0 to 5.4 years) and stratified according to successful chronic total occlusion (sCTO) or unsuccessful chronic total occlusion (uCTO) recanalization. Major adverse cardiac events (MACE) included myocardial infarction (MI), urgent revascularization, stroke, or death. RESULTS A total of 582 (69.6%) procedures were successful. Stents were implanted in 97.0% of successful procedures (mean: 2.3 ± 0.1 stents per patient, 73% drug-eluting). Prior revascularization was more frequent among uCTO patients: coronary artery bypass grafting (CABG) (16.5% vs. 7.4%; p < 0.0001), PCI (36.0% vs. 21.2%; p < 0.0001). Baseline characteristics were otherwise similar. Intraprocedural complications, including coronary dissection, were more frequent in unsuccessful cases (20.5% vs. 4.9%; p < 0.0001), but did not affect in-hospital MACE (3% vs. 2.1%; p = NS). All-cause mortality was 17.2% for uCTO and 4.5% for sCTO at 5 years (p < 0.0001). The need for CABG was reduced following sCTO (3.1% vs. 22.1%; p < 0.0001). Multivariate analysis demonstrated that procedural success was independently predictive of mortality (hazard ratio [HR]: 0.32 [95% confidence interval (CI): 0.18 to 0.58]), which persisted when incorporating a propensity score (HR: 0.28 [95% CI: 0.15 to 0.52]). CONCLUSIONS Successful CTO PCI is associated with improved survival out to 5 years. Adoption of techniques and technologies to improve procedural success may have an impact on prognosis.

Automated analysis of atrial late gadolinium enhancement imaging that correlates with endocardial voltage and clinical outcomes: A 2-center study

Background For late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) assessment of atrial scar to guide management and targeting of ablation in atrial fibrillation (AF), an objective, reproducible method of identifying atrial scar is required. Objective To describe an automated method for operator-independent quantification of LGE that correlates with colocated endocardial voltage and clinical outcomes. Methods LGE CMR imaging was performed at 2 centers, before and 3 months after pulmonary vein isolation for paroxysmal AF (n = 50). A left atrial (LA) surface scar map was constructed by using automated software, expressing intensity as multiples of standard deviation (SD) above blood pool mean. Twenty-one patients underwent endocardial voltage mapping at the time of pulmonary vein isolation (11 were redo procedures). Scar maps and voltage maps were spatially registered to the same magnetic resonance angiography (MRA) segmentation. Results The LGE levels of 3, 4, and 5SDs above blood pool mean were associated with progressively lower bipolar voltages compared to the preceding enhancement level (0.85 ± 0.33, 0.50 ± 0.22, and 0.38 ± 0.28 mV; P = .002, P < .001, and P = .048, respectively). The proportion of atrial surface area classified as scar (ie, >3 SD above blood pool mean) on preablation scans was greater in patients with postablation AF recurrence than those without recurrence (6.6% ± 6.7% vs 3.5% ± 3.0%, P = .032). The LA volume >102 mL was associated with a significantly greater proportion of LA scar (6.4% ± 5.9% vs 3.4% ± 2.2%; P = .007). Conclusions LA scar quantified automatically by a simple objective method correlates with colocated endocardial voltage. Greater preablation scar is associated with LA dilatation and AF recurrence.

Remote ischemic preconditioning has a neutral effect on the incidence of kidney injury after coronary artery bypass graft surgery

Acute kidney injury (AKI) is a frequent complication of cardiac surgery and usually occurs in patients with preexisting chronic kidney disease (CKD). Remote ischemic preconditioning (RIPC) may mitigate the renal ischemia-reperfusion injury associated with cardiac surgery and may be a preventive strategy for postsurgical AKI. We undertook a randomized controlled trial of RIPC to prevent AKI in 86 patients with CKD (estimated glomerular filtration rate under 60 ml/min per 1.73 m(2)) undergoing coronary artery bypass graft (CABG) surgery. Forty-three patients each were randomized to receive standard care with or without RIPC consisting of three 5-minute cycles of forearm ischemia followed by reperfusion. The primary end point was the development of AKI defined as an increase in serum creatinine concentration over 0.3 mg/dl within 48 h of surgery. Secondary end points included a comparison between the study and control groups of several serum biomarkers of renal injury including cystatin-C, neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 (IL-18), and urinary biomarkers including NGAL, IL-18, and kidney injury molecule-1 measured at 6, 12, and 24 h after CABG, and the 72-h serum troponin T concentration area under the curve as a marker of myocardial injury. Clinical and operative characteristics were similar between the preconditioned and control groups. AKI developed in 12 patients in both groups within 48 h of CABG. There were no significant differences between the two groups in the concentrations of any of the serum or urinary biomarkers of renal or cardiac injury after CABG. Thus, RIPC induced by forearm ischemia-reperfusion had no effect on the frequency of AKI after CABG in patients with CKD.

Randomized Phase 2 Trial of Intracoronary Nitrite During Acute Myocardial Infarction

Rationale: Preclinical evidence demonstrates that inorganic nitrite, after its in situ conversion to nitric oxide, attenuates consequent myocardial reperfusion injury. Objective: We investigated whether intracoronary injection of nitrite during primary percutaneous coronary intervention might improve infarct size in ST-elevated myocardial infarction. Methods and Results: Patients undergoing primary percutaneous coronary intervention (n=80) were randomized to receive intracoronary (10 mL) sodium nitrite (1.8 &mgr;mol) or NaCl (placebo) before balloon inflation. The primary end point was infarct size assessed by measuring creatine kinase release. Secondary outcomes included infarct size assessed by troponin T release and by cardiac MRI on day 2. Baseline characteristics were similar between the groups. No evidence of differences in creatine kinase release (P=0.92), troponin T (P=0.85), or cardiac MRI–assessed infarct size (P=0.254) were evident. In contrast, there was an improvement in myocardial salvage index (P=0.05) and reduction in major adverse cardiac event at 1 year (2.6% versus 15.8%; P=0.04) in the nitrite group. In a 66-patient subgroup with thrombolysis in myocardial infarction ⩽1 flow, there was reduced serum creatine kinase (P=0.030) and a 19% reduction in cardiac MRI–determined infarct size (P=0.034) with nitrite. No adverse effects of nitrite were detected. Conclusions: In this phase II study, intracoronary nitrite infusion did not alter infarct size, although a trend to improved myocardial salvage index and a significant reduction in major adverse cardiac event was evident. In a subgroup of patients with thrombolysis in myocardial infarction flow ⩽1, nitrite reduced infarct size and major adverse cardiac event and improved myocardial salvage index, indicating that a phase III clinical trial assessing intracoronary nitrite administration as an adjunct to percutaneous coronary intervention in ST-elevated myocardial infarction patients is warranted. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01584453.

Diagnostic Accuracy of Cardiac Magnetic Resonance Imaging in the Detection and Characterization of Left Atrial Catheter Ablation Lesions: A Multicenter Experience

MRI Detection of Left Atrial Ablation Lesions. Introduction: We tested the hypothesis that cardiovascular magnetic resonance (CMR) imaging can reliably distinguish the presence or absence of left atrial (LA) ablation lesions by blinded analysis of pre‐ and postablation imaging.

Safety and feasibility of hospital discharge 2 days following primary percutaneous intervention for ST-segment elevation myocardial infarction

Aim Primary percutaneous coronary intervention (PPCI) produces more effective coronary reperfusion and allows immediate risk stratification compared with fibrinolysis. We investigated the safety and feasibility of very early discharge at 2 days following PPCI in selected low-risk cases. Methods This was a prospective observational cohort study of 2779 patients who underwent PPCI between 2004 and 2011. Patients meeting the following criteria were deemed suitable for very early discharge; TIMI III flow, left ventricle (LF) ejection fraction >40%, and rhythmic and haemodynamic stability out to 48 h. Higher-risk patients who did not fulfil these criteria were discharged later according to physician preference. All patients were offered outpatient review by a multidisciplinary team. Endpoints included 30 day readmission rates and major adverse cardiac events (MACE) out to a median of 2.8 years (IQR range: 1.3–4.4 years). Results 1309 (49.3%) PPCI patients met very early discharge criteria, of whom 1117 (85.3%) were actually discharged at 2 days. 620 (23.4%) were discharged at 3 days, and 916 (34.5%) >3 days after admission (median 5, IQR: 4–8) days). Patients discharged at 2 days were younger, and had lower rates of diabetes, renal dysfunction, multivessel coronary artery disease, previous myocardial infarction, and previous coronary artery bypass surgery, compared with patients discharged later. 30-day readmission rates for non-MACE events were 4.8%, 4.9% and 4.6% for patients discharged 2 days, 3 days and >3 days after admission, respectively. MACE rates were lowest in patients discharged at 2 days (9.6%, 95% CI 4.7% to 16.6%) compared with patients discharged at 3 days (12.3% 95% CI 6.0% to 19.2%) and >3 days (28.6% 95% CI 22.9% to 34.7%, p<0.0001) after admission. Conclusions Our data suggest that discharge of low-risk patients 2 days after successful PPCI is feasible and safe. Over 40% of all patients with ST-elevation myocardial infarction may be suitable for early discharge with important implications for healthcare costs.

Randomized trial of combination cytokine and adult autologous bone marrow progenitor cell administration in patients with non-ischaemic dilated cardiomyopathy: the REGENERATE-DCM clinical trial

Aims The REGENERATE-DCM trial is the first phase II randomized, placebo-controlled trial aiming to assess if granulocyte colony-stimulating factor (G-CSF) administration with or without adjunctive intracoronary (IC) delivery of autologous bone marrow-derived cells (BMCs) improves global left ventricular (LV) function in patients with dilated cardiomyopathy (DCM) and significant cardiac dysfunction. Methods and results Sixty patients with DCM and left ventricular ejection fraction (LVEF) at referral of ≤45%, New York Heart Association (NYHA) classification ≥2 and no secondary cause for the cardiomyopathy were randomized equally into four groups: peripheral placebo (saline), peripheral G-CSF, peripheral G-CSF and IC serum, and peripheral G-CSF and IC BMC. All patients, except the peripheral placebo group, received 5 days of G-CSF. In the IC groups, this was followed by bone marrow harvest and IC infusion of cells or serum on Day 6. The primary endpoint was LVEF change from baseline to 3 months, determined by advanced cardiac imaging. At 3 months, peripheral G-CSF combined with IC BMC therapy was associated with a 5.37% point increase in LVEF (38.30% ± 12.97 from 32.93% ± 16.46 P = 0.0138), which was maintained to 1 year. This was associated with a decrease in NYHA classification, reduced NT-pro BNP, and improved exercise capacity and quality of life. No significant change in LVEF was seen in the remaining treatment groups. Conclusion This is the first randomized, placebo-controlled trial with a novel combination of G-CSF and IC cell therapy that demonstrates an improvement in cardiac function, symptoms, and biochemical parameters in patients with DCM.

A randomized double-blind control study of early intra-coronary autologous bone marrow cell infusion in acute myocardial infarction: the REGENERATE-AMI clinical trial

Abstract Aims Clinical trials suggest that intracoronary delivery of autologous bone marrow-derived cells (BMCs) 1–7 days post-acute myocardial infarction (AMI) may improve left ventricular (LV) function. Earlier time points have not been evaluated. We sought to determine the effect of intracoronary autologous BMC on LV function when delivered within 24 h of successful reperfusion therapy. Methods and results A multi-centre phase II randomized, double-blind, and placebo-controlled trial. One hundred patients with anterior AMI and significant regional wall motion abnormality were randomized to receive either intracoronary infusion of BMC or placebo (1:1) within 24 h of successful primary percutaneous intervention (PPCI). The primary endpoint was the change in left ventricular ejection fraction (LVEF) between baseline and 1 year as determined by advanced cardiac imaging. At 1 year, although LVEF increased compared with baseline in both groups, the between-group difference favouring BMC was small (2.2%; 95% confidence interval, CI: −0.5 to 5.0; P = 0.10). However, there was a significantly greater myocardial salvage index in the BMC-treated group compared with placebo (0.1%; 95% CI: 0.0–0.20; P = 0.048). Major adverse events were rare in both treatment groups. Conclusion The early infusion of intracoronary BMC following PPCI for patients with AMI and regional wall motion abnormality leads to a small non-significant improvement in LVEF when compared with placebo; however, it may play an important role in infarct remodelling and myocardial salvage. Clinical trial registration Clinicaltrials.gov NCT00765453 and EudraCT 2007-002144-16.

Diagnosis and management of patients with acute cardiac symptoms, troponin elevation and culprit-free angiograms

Patients with acute cardiac symptoms, elevated cardiac troponin and culprit-free angiograms comprise a significant proportion of patients admitted with presumed acute coronary syndromes (ACS). International guidelines recommend that these patients receive lifelong secondary prevention under the presumption that angiographically undetectable coronary artery disease is the likeliest cause for their presentation. Recent studies using cardiac MRI suggest myocarditis to be the most common cause of these presentations. Emerging data also suggest that myocarditis presenting like an ACS may not be benign. In this article the current literature on patients presenting with acute cardiac symptoms, elevated cardiac troponins but culprit-free angiograms is reviewed, focusing on the diagnostic utility of cardiac MRI in this cohort, and the importance of diagnosing acute myocarditis. The development of higher sensitivity troponin assays will undoubtedly lead to an increase in the number of patients with presumed ACS but culprit free angiography. Robust management pathways including cardiac MRI are vital for cardiac centres dealing with these patients in order to achieve cost-effective, individualised patient care.

Characteristics and Outcomes of Dialysis Patients with Infective Endocarditis

Background: The incidence of infective endocarditis (IE) in dialysis patients is higher than the general population. Dialysis patients who develop endocarditis are thought to have a poorer prognosis than other patients with IE. Aim: To examine the risk profiles, clinical features, and outcomes of patients on dialysis who developed IE in a large cohort. Design and Methods: A retrospective analysis of all patients developing IE on dialysis (using the modified Duke criteria) was undertaken between 1998 and 2011. Patients were identified from a prospectively collected clinical database. Results: 42 patients developed IE out of a total incident dialysis population of 1,500 over 13 years. 95% of the patients (40/42) were on long-term haemodialysis (HD) and 5% (2/42) on peritoneal dialysis. Mean patient age was 55.2 years (IQR: 43-69), and mean duration of HD prior to IE was 57.4 months. Primary HD access at the time of diagnosis was an arteriovenous fistula in 35% (14/40), a dual-lumen tunnelled catheter in 55% (22/40), and a dual-lumen non-tunnelled catheter in 10% (4/40). Staphylococcus aureus (including methicillin-resistant S. aureus) was present in 57.1% (24/42). The aortic valve was affected in 42.8% of the patients (18/42), the mitral valve in 30.9% (13/42), and both valves in 9.5% (4/42). 33.3% of the patients had an abnormal valve before the episode of IE. In 21.4% (9/42), valve surgery was performed and mortality was lower in the surgical group compared to the group managed medically during hospitalisation (11.1 vs. 15.2%, p = 0.892), at 3 months (13.1 vs. 19.6%, p = 0.501), and during follow-up (p = 0.207), but this difference did not reach statistical significance. Age >60 years, septic emboli, and methicillin-resistant S. aureus were all adverse prognostic factors. Patients receiving surgery were younger (mean 47.1 ± 14.4 years vs. 57.4 ± 14.3, p = 0.049) and less likely to be infected with S. aureus (surgery 33.3% vs. antibiotics 63.6%, p = 0.046). Conclusion: This is one of the largest reported series of IE in dialysis patients. The incidence of IE remains high and the prognosis poor in dialysis patients, although patients selected for early valve surgery have good 1-year survival.