Dominic Y. Leung

Background: While many studies have suggested that heart failure (HF) may lead to cognitive impairment, our understanding about this relationship is limited. This study investigated the association of cognitive function with HF risk factors and how cognitive impairment may impact the development of incident clinical HF in people with subclinical HF. Methods: People with either preclinical (at risk and asymptomatic, n=814) or clinical (symptomatic, n=1152) HF were recruited from communities, clinics, and hospitals in 5 Australian states (Victoria, New South Wales, South Australia, Tasmania, and Queensland). Cognitive impairment was measured with the Montreal Cognitive Assessment (MOCA P P =0.042) with clinical HF. Of patients with preclinical HF at baseline, 71 (9%) developed clinical HF and 87 (11%) died within the follow‐up period. In time‐to‐event analysis of participants with preclinical HF, those with either cognitive impairment or left ventricular dysfunction had double the risk of developing clinical HF, compared with those with normal cognition and left ventricular function. Those with concomitant cognitive impairment and left ventricular dysfunction had a 4‐fold greater risk of developing HF (subdistribution hazard ratio, 4.01 [95% CI, 2.39–6.76]). Conclusions: Cognitive impairment is associated with increased risk of incident clinical HF, independent of cardiac function and other HF risk factors.

Introduction: Percutaneous coronary intervention (PCI) is performed by interventional cardiologists who, over their career, are exposed to substantial X-ray radiation and also face potential musculoskeletal injuries from the prolonged wearing of heavy protective equipment. Patients are also at risk from radiation exposure. Robotic-assisted PCI (R-PCI) allows millimetre control of the coronary guide-catheter, guidewires and intracoronary devices via three joysticks and touchscreens located within in a shielded ‘cockpit’, away from radiation. Initial studies have demonstrated efficacy and safety of R-PCI with significant radiation reductions. However, these studies are non-randomised, registry based or observational data with short clinical follow-up. We aim to perform the first randomised controlled trial investigating R-PCI compared with manual PCI (M-PCI) with longer clinical follow-up. Methods and analysis: The Percutaneous coronary intervention using Assisted Robotic TechnologY (PARTY) trial is a single-centre, prospective, randomised, open-label clinical trial comparing R-PCI to M-PCI. Eligible patients between 18 and 85 years undergoing coronary angiography, and are subsequently deemed to require PCI, will be screened. A key exclusion criterion is if the operator determines that the participant or coronary anatomy is unsuitable for R-PCI. Patients will be randomised to R-PCI or M-PCI in a 1:1 fashion. The primary outcome is radiation exposure to the patient, as measured by personal radiation dosimeters. Other procedural, safety and efficacy outcomes will be compared. Patients will be followed up until hospital discharge (or 72 hours, whichever occurs first), and then by telephone at 30 and 365 days. Trial registration number: ACTRN12623000480684.

Objectives: We examined the appropriateness of prehospital cardiac catheter laboratory activation (CCL‐A) in ST‐segment elevation myocardial infarction (STEMI) utilizing the University of Glasgow algorithm (UGA) and remote interventional cardiologist consultation.Background: The incremental benefit of prehospital electrocardiogram (PH‐ECG) transmission on the diagnostic accuracy and appropriateness of CCL‐A has been examined in a small number of studies with conflicting results.Methods: We identified consecutive PH‐ECG transmissions between June 2, 2010 and October 6, 2016. Blinded adjudication of ECGs, appropriateness of CCL‐A, and index diagnoses were performed using the fourth universal definition of MI. The primary outcome was the appropriate CCL‐A rate. Secondary outcomes included rates of false‐positive CCL‐A, inappropriate CCL‐A, and inappropriate CCL nonactivation.Results: Among 1088 PH‐ECG transmissions, there were 565 (52%) CCL‐As and 523 (48%) CCL nonactivations. The appropriate CCL‐A rate was 97% (550 of 565 CCL‐As), of which 4.9% (n = 27) were false‐positive. The inappropriate CCL‐A rate was 2.7% (15 of 565 CCL‐As) and the inappropriate CCL nonactivation rate was 3.6% (19 of 523 CCL nonactivations). Reasons for appropriate CCL nonactivation (n = 504) included nondiagnostic ST‐segment elevation (n = 128, 25%), bundle branch block (n = 132, 26%), repolarization abnormality (n = 61, 12%), artefact (n = 72, 14%), no ischemic symptoms (n = 32, 6.3%), severe comorbidities (n = 26, 5.2%), transient ST‐segment elevation (n = 20, 4.0%), and others.Conclusions: PH‐ECG interpretation utilizing UGA with interventional cardiologist consultation accurately identified STEMI with low rates of inappropriate and false‐positive CCL‐As, whereas using UGA alone would have almost doubled CCL‐As. The benefits of cardiologist consultation were identifying “masquerading” STEMI and avoiding unnecessary CCL‐As.

Background: Patients with suspected ST‐segment–elevation myocardial infarction (STEMI) and cardiac catheterization laboratory nonactivation (CCL‐NA) or cancellation have reportedly similar crude and higher adjusted risks of death compared with those with CCL activation, though reasons for these poor outcomes are not clear. We determined late clinical outcomes among patients with prehospital ECG STEMI criteria who had CCL‐NA compared with those who had CCL activation. Methods and Results: We identified consecutive prehospital ECG transmissions between June 2, 2010 to October 6, 2016. Diagnoses according to the Fourth Universal Definition of myocardial infarction (MI), particularly rates of myocardial injury, were adjudicated. The primary outcome was all‐cause death. Secondary outcomes included cardiovascular death/MI/stroke and noncardiovascular death. To explore competing risks, cause‐specific hazard ratios (HRs) were obtained. Among 1033 included ECG transmissions, there were 569 (55%) CCL activations and 464 (45%) CCL‐NAs (1.8% were inappropriate CCL‐NAs). In the CCL activation group, adjudicated index diagnoses included MI (n=534, 94%, of which 99.6% were STEMI and 0.4% non‐STEMI), acute myocardial injury (n=15, 2.6%), and chronic myocardial injury (n=6, 1.1%). In the CCL‐NA group, diagnoses included MI (n=173, 37%, of which 61% were non‐STEMI and 39% STEMI), chronic myocardial injury (n=107, 23%), and acute myocardial injury (n=47, 10%). At 2 years, the risk of all‐cause death was higher in patients who had CCL‐NA compared with CCL activation (23% versus 7.9%, adjusted risk ratio, 1.58, 95% CI, 1.24–2.00), primarily because of an excess in noncardiovascular deaths (adjusted HR, 3.56, 95% CI, 2.07–6.13). There was no significant difference in the adjusted risk for cardiovascular death/MI/stroke between the 2 groups (HR, 1.23, 95% CI, 0.87–1.73). Conclusions: CCL‐NA was not primarily attributable to missed STEMI, but attributable to “masquerading” with high rates of non‐STEMI and myocardial injury. These patients had worse late outcomes than patients who had CCL activation, mainly because of higher rates of noncardiovascular deaths.

Clinical trials traditionally aim to show a new treatment is superior to placebo or standard treatment, that is, superiority trials. There is an increasing number of trials demonstrating a new treatment is non-inferior to standard treatment. The hypotheses, design and interpretation of non-inferiority trials are different to superiority trials. Non-inferiority trials are designed with the notion that the new treatment offers advantages over standard treatment in certain important aspects. The non-inferior margin is a predetermined margin of difference between the new and standard treatment that is considered acceptable or tolerable for the new treatment to be considered ‘similar’ or ‘not worse’. Both relative difference and absolute difference methods can be used to define the non-inferior margin. Sequential testing for non-inferiority and superiority is often performed. Non-inferiority trials may be necessary in situations where it is no longer ethical to test any new treatment against placebo. There are inherent assumptions in non-inferiority trials which may not be correct and which are not being tested. Successive non-inferiority trials may introduce less and less effective treatments even though these treatments may have been shown to be non-inferior. Furthermore, poor quality trials favour non-inferior results. Intention-to-treat analysis, the preferred way to analyse randomised trials, may favour non-inferiority. Both intention-to-treat and per-protocol analyses should be recommended in non-inferiority trials. Clinicians should be aware of the pitfalls of non-inferiority trials and not accept non-inferiority on face value. The focus should not be on the p values but on the effect size and confidence limits.

An impaired contractile reserve (CR) may be an early manifestation of left ventricular (LV) systolic dysfunction in hypertensive patients. Using normotensive patients as controls, we examined LV CR and its correlates in hypertensive patients. One hundred and twenty-nine (68 men, aged 58.6 ± 9.5 years, 73 had hypertension) patients underwent dobutamine echocardiography. Patients with significant coronary or valvular disease, previous myocardial infarction or revascularization, and diabetes were excluded. LV ejection fraction (LVEF), global longitudinal strain (GLS), circumferential, and radial strain were measured at rest and at low-dose dobutamine. Absolute CR was calculated as the difference in LVEF and multi-directional strain between low-dose dobutamine and their corresponding resting values. Relative CR is the ratio of absolute CR to their corresponding resting values. Hypertensive patients, compared with controls, have significantly impaired GLS at rest (−16.8 ± 2.2% vs. −19.6 ± 1.5%, P < 0.0001) and at low-dose dobutamine (−17.9 ± 2.7% vs. −22.8 ± 2.6%, P < 0.0001). Absolute and relative GLS CR were significantly lower in hypertensive patients (−1.1 ± 2.1% vs. −3.2 ± 2.2% and 7.4 ± 13.9% vs. 16.4 ± 11.7%, respectively, both P < 0.001). Circumferential strain was preserved at rest but impaired at low-dose dobutamine in hypertensive patients (−23.0 ± 4.1% vs. −25.2 ± 3.4%, P = 0.002). There were no differences in LVEF or radial strain between the groups. LV wall thickness and systolic blood pressure correlated significantly with GLS at rest and at low-dose dobutamine. LV wall thickness is the only independent correlates of absolute CR. Compared with controls, hypertensive patients have impaired LV GLS at rest and impaired CR despite normal LVEF. Impaired CR correlated with LV wall thickness but independent of prevailing blood pressure.