Mixed plaque on coronary CT angiography predicts atherosclerotic events in asymptomatic intermediate-risk individuals.

OBJECTIVE: Coronary CT angiography (CCTA) permits both qualitative and quantitative analysis of atherosclerotic plaque and may be a suitable risk modifier in assessing patients at intermediate risk of atherosclerotic cardiovascular disease. We sought to determine the association of plaque components with long-term major adverse cardiovascular events (MACEs) in asymptomatic intermediate-risk patients, compared with conventional coronary artery calcium (CAC) score. METHODS: 100 intermediate-risk patients underwent double-blinded CCTA. Follow-up was conducted at 10 years and data were cross-referenced with the National Death Index. The primary outcome was MACE, which was a composite of death, acute coronary syndrome (ACS), revascularisation and stroke. RESULTS: The median time from CCTA to follow-up was 9.5 years. 83 patients completed follow-up interview and mortality data were available on all 100 patients. MACE occurred in 17 (20.5%) patients, which included 2 (2%) deaths, 8 (10%) ACS, 3 (4%) strokes and 5 (6%) revascularisation procedures. 47 (57%) patients had mixed plaque, which was predictive of MACE (OR 4.68 (95% CI 1.19 to 18.5) p=0.028). The burden of non-calcified and mixed plaque, defined by non-calcified plaque segment stenosis score, was also a predictor of long-term MACE (OR 1.59 (95% CI 1.18 to 2.13) p=0.002). Neither calcified plaque (OR 3.92 (95% CI 0.80 to 19.3)) nor CAC score (OR 1.01 (95% CI 0.999 to 1.02)) was associated with long-term MACE. CONCLUSION: The presence and burden of mixed plaque on CCTA is associated with an increased risk of long-term MACE among asymptomatic intermediate-risk patients and is a superior predictor to CAC score.

Impact of Preprocedural Diastolic Blood Pressure on Outcomes in Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Recent US guidelines recommend lower blood pressure (BP) targets in hypertension, but aggressive lowering of diastolic BP (DBP) can occur at the expense of myocardial perfusion, particularly in the presence of coronary artery disease. We sought to establish the long-term impact of low DBP on mortality among patients undergoing percutaneous coronary intervention with well-controlled systolic BP. METHODS: We analyzed data from 12 965 patients undergoing percutaneous coronary intervention between 2009 and 2018 from the Melbourne Interventional Group registry who had a preprocedural systolic BP of ≤140 mm Hg. Patients with ST-elevation myocardial infarction, cardiogenic shock, and out-of-hospital arrest were excluded. Patients were stratified into 5 groups according to preprocedural DBP: <50, 50 to 59, 60 to 69, 70 to 79, and ≥80 mm Hg. The primary outcome was long-term, all-cause mortality. Mortality data were derived from the Australian National Death Index. RESULTS: Patients with DBP<50 mm Hg were older with higher rates of diabetes, renal impairment, prior myocardial infarction, left ventricular dysfunction, peripheral and cerebrovascular disease (all P<0.001). Patients with DBP<50 mm Hg had higher 30-day (2.5% versus 0.7% for the other 4 quintiles; P<0.0001) and long-term mortality (median, 3.6 years; follow-up, 29% versus 11%; P<0.0001). Cox-regression analysis revealed that DBP<50 mm Hg was an independent predictor of long-term mortality (hazard ratio [HR], 1.55 [95% CI, 1.20-2.00]; P=0.001). CONCLUSIONS: In patients with well-controlled systolic BP undergoing percutaneous coronary intervention, low DBP (<50 mm Hg) is an independent predictor of long-term mortality.

Spontaneous Coronary Artery Dissection in an Orthotopic Heart Transplant Recipient.

We present the case of acute myocardial infarction secondary to spontaneous coronary artery dissection in a patient 2 weeks post orthotopic heart transplantation. (Level of Difficulty: Advanced.).

Sex disparity in secondary prevention pharmacotherapy and clinical outcomes following acute coronary syndrome.

AIMS: We sought to investigate if sex disparity exists for secondary prevention pharmacotherapy following acute coronary syndrome (ACS) and impact on long-term clinical outcomes. METHODS AND RESULTS: We analysed data on medical management 30-day post-percutaneous coronary intervention (PCI) for ACS in 20 976 patients within the multicentre Melbourne Interventional Group registry (2005-2017). Optimal medical therapy (OMT) was defined as five guideline-recommended medications, near-optimal medical therapy (NMT) as four medications, sub-optimal medical therapy (SMT) as ≤3 medications. Overall, 65% of patients received OMT, 27% NMT and 8% SMT. Mean age was 64 ± 12 years; 24% (4931) were female. Women were older (68 ± 12 vs. 62 ± 12 years) and had more comorbidities. Women were less likely to receive OMT (61% vs. 66%) and more likely to receive SMT (10% vs. 8%) compared to men, P < 0.001. On long-term follow-up (median 5 years, interquartile range 2-8 years), women had higher unadjusted mortality (20% vs. 13%, P < 0.001). However, after adjusting for medical therapy and baseline risk, women had lower long-term mortality [hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.79-0.98; P = 0.02]. NMT (HR 1.17, 95% CI 1.05-1.31; P = 0.004) and SMT (HR 1.79, 95% CI 1.55-2.07; P < 0.001) were found to be independent predictors of long-term mortality. CONCLUSION: Women are less likely to be prescribed optimal secondary prevention medications following PCI for ACS. Lower adjusted long-term mortality amongst women suggests that as well as baseline differences between gender, optimization of secondary prevention medical therapy amongst women can lead to improved outcomes. This highlights the need to focus on minimizing the gap in secondary prevention pharmacotherapy between sexes following ACS.

Iron deficiency in heart failure with preserved ejection fraction: a systematic review and meta-analysis.

Objective: Iron deficiency (ID) has an established impact on outcomes in patients with heart failure with reduced ejection fraction; however, there is a lack of conclusive evidence in patients with heart failure with preserved ejection fraction (HFpEF). We sought to clarify the prevalence and impact of ID in patients with HFpEF. Methods: A systematic search of Cohcrane, MEDLINE, EMBASE, Web of Science and CINAHL electronic databases was performed to identify relevant studies. Included studies defined HFpEF as heart failure with an ejection fraction ≥50%. We used a random-effects meta-analysis to determine the composite prevalence of ID in patients with HFpEF across the included studies. Other outcomes were assessed with qualitative analysis due to a paucity of studies with comparable outcome measures. Results: The prevalence of ID in the included studies was 59% (95% CI 52% to 65%). ID was associated with lower VO2 max in three of four studies reporting VO2 max as an outcome measure, lower functional status as determined by dyspnoea class or 6 min walk test in two of three studies, and worse health-related quality of life in both studies reporting on this outcome. Conversely, ID had no impact on death or hospitalisation in three of the four studies investigating this. Conclusions: ID is highly prevalent in patients with HFpEF and is associated with worse exercise capacity and functional outcomes, but not hospitalisation or mortality. Our study establishes that ID may play an important a role in HFpEF.

Impact of Pre-Procedural Blood Pressure on Long-Term Outcomes Following Percutaneous Coronary Intervention.

BACKGROUND: High systolic blood pressure (SBP) increases cardiac afterload, whereas low diastolic blood pressure (DBP) may lead to impaired coronary perfusion. Thus, wide pulse pressure (high systolic, low diastolic [HSLD]) may contribute to myocardial ischemia and also be a predictor of adverse cardiovascular events. OBJECTIVES: The purpose of this study was to determine the relationship between pre-procedural blood pressure and long-term outcome following percutaneous coronary intervention (PCI). METHODS: The study included 10,876 consecutive patients between August 2009 and December 2016 from the Melbourne Interventional Group registry undergoing PCI with pre-procedural blood pressure recorded. Patients with ST-segment elevation myocardial infarction, cardiogenic shock, and out-of-hospital cardiac arrest were excluded. Patients were divided into 4 groups according to SBP (high ≥120 mm Hg, low <120 mm Hg) and DBP (high >70 mm Hg, low ≤70 mm Hg). RESULTS: Mean pulse pressure was 60 ± 21 mm Hg. Patients with HSLD were older and more frequently women, with higher rates of hypercholesterolemia, renal impairment, diabetes, and multivessel and left main disease (all p ≤ 0.0001). There was no difference in 30-day major adverse cardiac events, but at 12 months the HSLD group had a greater incidence of myocardial infarction (p = 0.018) and stroke (p = 0.013). Long-term mortality was highest for HSLD (7.9%) and lowest for low systolic, high diastolic (narrow pulse pressure) at 2.1% (p = 0.0002). Cox regression analysis demonstrated significantly lower long-term mortality in the low systolic, high diastolic cohort (hazard ratio: 0.50; 99% confidence interval: 0.25 to 0.98; p = 0.04). CONCLUSIONS: Pulse pressure at the time of index PCI is associated with long-term outcomes following PCI. A wide pulse pressure may serve as a surrogate marker for risk following PCI and represents a potential target for future therapies.

Trends and Clinical Outcomes in Patients Undergoing Primary Percutaneous Revascularisation for ST-Elevation Myocardial Infarction: A Single Centre Experience.

BACKGROUND: Primary percutaneous coronary intervention (PPCI) is the preferred therapy for patients presenting with ST-elevation myocardial infarction (STEMI). We reviewed patients undergoing PCI for STEMI over a 6-year period to evaluate changes in procedural characteristics and clinical outcomes given recent changes to STEMI guidelines. METHODS: All patients presenting to the Alfred Hospital, a tertiary referral hospital, between 1 January 2010 and 31 December 2015 undergoing PCI for STEMI were identified. Detailed review of their procedure reports was performed and 30-day and 12-month clinical outcomes were recorded including major adverse cardiac events (MACE). RESULTS: There was a total of 445 patients aged 60.6±12.4 years with 369 (82.9%) male. There was a significant increase in radial access use over the 6-year period 0/49 (0%) in 2010 vs 56/113 (49.6%) in 2015 (p<0.01). There was a significant reduction in the use of IIb/IIIa receptor antagonists during the period 29/49 (59%) in 2010 vs 24/113 (21%) in 2015 (p<0.01) and use of aspiration thrombectomy 15/49 (31%) in 2010 vs 19/113 (17%) in 2015 (p<0.01). There was no significant reduction in major bleeding over this period with 2/49 (4%) in 2010 vs 5/108 (5%) in 2015 (p=0.32). Thirty-day and 12-month mortality was also unchanged. CONCLUSION: Between 2010 and 2015 there has been a significant increase in the use of radial access and a reduction in the use of glycoprotein IIb/IIIa antagonists and aspiration thrombectomy in patients undergoing PPCI. This was not associated with changes in major bleeding or 30-day or 12-month mortality.

Incidence and impact of acute kidney injury in patients with acute coronary syndromes treated with coronary artery bypass grafting: Insights from the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) and Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trials.

BACKGROUND: Acute kidney injury (AKI) is a well-recognized predictor of morbidity and mortality after percutaneous coronary intervention. However, the impact of AKI on the outcome of patients with acute coronary syndromes (ACS) in relation to coronary artery bypass grafting (CABG) has not been established. METHODS: Of the 17,421 patients who presented with non-ST-segment elevation ACS or ST-segment elevation myocardial infarction enrolled in the ACUITY and HORIZONS-AMI trials, 1,406 (8.0%) underwent CABG as principal treatment after coronary angiography. End points were measured at 1 month and 1 year and included death, myocardial infarction, and ischemia-driven target vessel revascularization. Acute kidney injury was defined as a rise in creatinine of ≥ 0.5 mg/dL, or > 25%, from baseline at initial angiography. RESULTS: Acute kidney injury occurred during hospital admission in 449 (31.9%) of the 1,406 patients treated with CABG. One-month and 1-year mortality was 6.7% vs 2.2% (P < .0001) and 10.4% vs 4.3% (P < .0001) for patients with vs without AKI, respectively. Analogously, the 1-month and 1-year incidence of composite major adverse cardiac events (MACEs; death, MI, or target vessel revascularization) was 17.6% vs 12.4% (P = .003) and 22.0% vs 15.3% (P = .002) for patients with vs without AKI, respectively. After adjustment for age, sex, race, diabetes, hypertension, and baseline creatinine clearance, AKI was an independent predictor of mortality (overall and cardiac-related) and MACE at both 1 month and 1 year in patients treated with CABG. CONCLUSIONS: Acute kidney injury occurred in approximately 1 of every 3 patients with ACS treated with CABG and is a powerful independent predictor of death and MACE. These data highlight the need for AKI prevention strategies in patients undergoing CABG.

Impact of Contrast-Induced Acute Kidney Injury After Percutaneous Coronary Intervention on Short- and Long-Term Outcomes: Pooled Analysis From the HORIZONS-AMI and ACUITY Trials.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI), defined as a serum creatinine increase ≥0.5 mg/dL or ≥25% within 72 hours after contrast exposure, is a common complication of procedures requiring contrast media and is associated with increased short- and long-term morbidity and mortality. Few studies describe the effects of CI-AKI in a large-scale acute coronary syndrome population, and the relationship between CI-AKI and bleeding events has not been extensively explored. We sought to evaluate the impact of CI-AKI after percutaneous coronary intervention in patients presenting with acute coronary syndrome. METHODS AND RESULTS: We pooled patient-level data for 9512 patients from the percutaneous coronary intervention cohorts of the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) and Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) multicenter randomized trials. Patients were classified according to CI-AKI development, and cardiovascular outcomes at 30 days and 1 year were compared between groups. A total of 1212 patients (12.7%) developed CI-AKI. Patients with CI-AKI were older, with a more extensive comorbidity profile than without CI-AKI. Multivariable analysis confirmed several previously identified predictors of CI-AKI, including diabetes mellitus, contrast volume, age, and baseline hemoglobin. Mortality rates were significantly higher in the CI-AKI group at 30 days (4.9% versus 0.7%; P<0.0001) and 1 year (9.8% versus 2.9%; P<0.0001), as were rates of 1-year myocardial infarction, definite/probable stent thrombosis, target lesion revascularization, and major adverse cardiac events. Major bleeding (13.8% versus 5.4%; hazard ratio, 2.64; 95% confidence interval, 2.21-3.15; P<0.0001) was also higher in patients with CI-AKI. After multivariable adjustment, results were unchanged. CONCLUSIONS: CI-AKI after percutaneous coronary intervention in patients presenting with acute coronary syndrome is independently associated with increased risk of short- and long-term ischemic and hemorrhagic events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00433966 (HORIZONS-AMI) and ACUITY (NCT00093158).

Resistant hypertension and renal denervation where to now?

Treatment resistant hypertension (TRH) is a major clinical problem with limited treatment options. Renal denervation (RDN) arose as a safe and very effective treatment for TRH with early studies showing dramatic blood pressure reductions however subsequent studies have not shown such a benefit. This review discusses the pathophysiology of TRH and the results of the published studies in RDN for TRH. The initial symplicity (1 and 2) studies using the Ardian RDN catheter showed that office blood pressures were significantly reduced 6 months following the procedure. However these initial studies were limited by a lack of a true control group and inadequate blinding. Subsequent studies (symplicity 3 and simplicity flex) included patients with elevated blood pressures on 24 hr ambulatory blood pressure monitor as well as office measurements. Furthermore, both included a sham arm where patients were randomized to undergo renal angiography alone or RDN, patients were blinded to whether they were in the treatment or sham arm. These more recent studies showed that in both the control and treatment group while there was a significant BP reduction from baseline there was no difference between the groups. Thus RDN appears to have no benefit in blood pressure reduction in those with TRH. RDN currently should only be used in patients with TRH as part of a properly designed clinical study. Pre clinical data suggests that renal sympathetic overactivity is an issue in younger hypertensive patients and this may be the group in which future studies using RDN should focus.

Incidence and impact of totally occluded culprit coronary arteries in patients presenting with non-ST-segment elevation myocardial infarction.

The accuracy of the 12-lead electrocardiogram in detecting coronary artery occlusion is limited. We sought to determine the incidence, distribution, and outcomes of patients who have total occlusion of the culprit artery but present with non-ST-segment elevation myocardial infarction (NSTEMI). The randomized Acute Catheterization and Urgent Intervention Triage Strategy trial enrolled 13,819 patients presenting with non-ST-segment elevation acute coronary syndromes who underwent an early invasive strategy. The present study includes 1,319 patients with baseline biomarker elevation (NSTEMI) and no history of coronary artery bypass graft who underwent percutaneous coronary intervention of a single culprit vessel. We compared the baseline characteristics and outcomes according to whether the culprit vessel was occluded (baseline Thrombolysis In Myocardial Infarction [TIMI] 0 to 1) or patent (TIMI 2 to 3 flow) by angiographic core laboratory assessment. TIMI 0 to 1 flow in the culprit artery was present in 262 of 1,319 (19.9%) patients. The incidence of coronary occlusion was 28.4%, 19.3%, and 12.6% in patients with NSTEMI because of right coronary, left circumflex, and left anterior descending artery disease, respectively. Patients with an occluded culprit artery were more commonly men and had ST-segment deviation ≥1 mm. One-year outcomes, including death (3.5% vs 3.0%, p = 0.68) and myocardial infarction (8.4% vs 9.6%, p = 0.47), did not differ significantly between patients with versus without occluded culprit arteries, respectively. In conclusion, the present study demonstrates that the culprit artery is totally occluded in approximately 1 in 5 patients presenting with NSTEMI and single-vessel disease; however, the presence of total occlusion in NSTEMI was not associated with an incremental hazard of death or reinfarction at 1 year.

Antiplatelet therapy after drug-eluting stent implantation.

Dual antiplatelet therapy (DAPT), which is the combination of aspirin and a platelet P2Y12 inhibitor, is the cornerstone of secondary prevention in ischemic heart disease requiring intracoronary stenting. Although the efficacy of DAPT in the reduction of ischemic events has been well validated, the optimal duration, and indeed combination, of therapy is yet to be established. This area continues to attract debate with new developments in stent design and antiplatelet agents, as well as evolving clinical skill levels. Presently, clinical guidelines advocate the use of DAPT for 6-12 months following drug-eluting stent (DES) implantation, but this can vary according to clinical indication, bleeding risk, and country of practice. Concerns have arisen that unnecessary prolongation of DAPT may be associated with increased bleeding events, as well as cost. Whether these guidelines effectively cater to current stenting techniques, devices, and antiplatelet agents remains to be determined. This review analyzes contemporary issues surrounding DAPT following DES implantation, as researchers continue to seek to strike the optimal balance between bleeding and thrombotic risk. Although reduced DAPT durations continue to show promising results in preventing ischemic events while also mitigating bleeding risk, ultimately the consideration of clinical presentation as well as medical and social history is paramount to guiding the optimal duration and cessation of DAPT.