Do the Few Dictate Care for the Many? Revascularisation Considerations That Go Beyond the Guidelines.

The burden of coronary artery disease (CAD) is large and growing, commonly presenting with comorbidities and older age. Patients may benefit from coronary revascularisation with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), yet half of patients with CAD who would benefit from revascularisation fall outside the eligibility criteria of trials to date. As such, the choice of revascularisation procedures varies depending on the CAD anatomy and complexity, surgical risk and comorbidities, the patient's preferences and values, and the treating team's expertise. The recent American guidelines on coronary revascularisation are comprehensive in describing recommendations for PCI, CABG, or conservative management in patients with CAD. However, individual challenging patient presentations cannot be fully captured in guidelines. The aim of this narrative review is to summarise common clinical scenarios that are not sufficiently described by contemporary clinical guidelines and trials in order to inform heart team members and trainees about the nuanced considerations and available evidence to manage such cases. We discuss clinical cases that fall beyond the current guidelines and summarise the relevant evidence evaluating coronary revascularisation for these patients. In addition, we highlight gaps in knowledge based on a lack of research (eg, ineligibility of certain patient populations), underrepresentation in research (eg, underenrollment of female and non-White patients), and the surge in newer minimally invasive and hybrid techniques. We argue that ultimately, evidence-based medicine, patient preference, shared decision making, and effective heart team communications are necessary to best manage complex CAD presentations potentially benefitting from revascularisation with CABG or PCI.

Trajectories of P2Y12 inhibitor adherence in patients with acute coronary syndromes.

PURPOSE: P2Y12 inhibitors (P2Y12i) reduce cardiac events after acute coronary syndromes (ACS). However, suboptimal P2Y12i adherence persists. We aimed to examine P2Y12i non-adherence using group-based trajectory methods and to identify adherence predictors. METHODS: We conducted a population-based, retrospective cohort study using administrative data in Ontario, Canada of patients ≥65 years admitted for ACS between April 2014 and March 2018 with a P2Y12i dispensed within 7 days of discharge. We used group-based trajectory models to characterize longitudinal 1-year adherence patterns. Predictors associated with each adherence trajectory were identified by multinomial logistic regression. RESULTS: We included 11 917 patients using clopidogrel and 9763 using ticagrelor, aged [mean ± SD]: 77.33 ± 8.31/73.59 ± 6.79 years; men: 56.2%/65.4%, respectively. We identified 3 longitudinal adherence trajectories, that differed by agent: 75% of clopidogrel and 68% of ticagrelor patients showed a consistently adherent trajectory, while 13%/17% were gradually, and 12%/15% were rapidly non-adherent, respectively (p < 0.001). Differing baseline characteristics in each cohort were associated with observed adherence trajectories. Concomitant atrial fibrillation and prior bleeding history were associated with non-adherence among clopidogrel users. Among ticagrelor users, women and older persons were more likely to be rapidly non-adherent, adherence declining steeply starting 1 month post-ACS. CONCLUSIONS: We identified distinct adherence trajectories for clopidogrel and ticagrelor post-ACS, with 3 out of 4 clopidogrel patients but only 2 out of 3 ticagrelor patients in the consistently adherent trajectory. Intensive interventions targeted to the period of steep adherence decline post-ACS, particularly for women and older persons initiating ticagrelor, and patients with atrial fibrillation on clopidogrel should be considered and investigated further.

Clinical Outcomes in Younger Women Hospitalized With an Acute Myocardial Infarction: A Contemporary Population-Level Analysis.

BACKGROUND: For younger women with acute myocardial infarction (AMI), little is known regarding their contemporary care pathways and clinical outcomes. METHODS: We studied AMI patients aged 18-55 years, hospitalized from April 1, 2009, to March 31, 2019, in Ontario, Canada. We compared trends in comorbidities, angiographic findings, and revascularisation rates in men and women. The primary outcome was 1-year all-cause mortality or readmission for unstable angina, AMI, heart failure, or stroke. Inverse probability of treatment weighting was used to account for differences in baseline clinical characteristics between men and women. RESULTS: Among the 38,071 AMI patients included, 8,077 (21.2%) were women. Over the study period, women had increasing rates of diabetes (24.8% to 34.9%; Ptrend < 0.001), and declining rates of smoking (53.2% to 41.7%; Ptrend < 0.005). Although most patients received coronary angiography (96%), coronary revascularisation was less frequent among women than men (percutaneous coronary intervention: 61.9% vs 78.8% [P < 0.001]; surgery: 4.1% vs 6.0% [P < 0.001]). Women had more normal coronary anatomy (5.8% vs 1.7%; P < 0.001) and nonobstructive disease (22.8% vs 9.3%; P < 0.001) than men. Compared with men, the primary composite end point was significantly increased among women (10.0% vs 7.9%, adjusted HR 1.11; P = 0.02) and related to increased readmission rates for cardiovascular events. All-cause readmission was significantly increased among women (25.8% vs 21.1%, adjusted HR 1.34; P < 0.0001). CONCLUSIONS: Coronary angiography is performed almost universally in younger women with AMI; however, coronary revascularisation is less frequent, perhaps reflecting less obstructive disease. Although mortality rates after AMI were similar between sexes, cardiovascular readmission rates and all-cause readmissions were significantly increased among women.

Optimizing the management of patients with small renal masses in a Canadian context: A Markov decision-analysis model.

INTRODUCTION: The management of patients with a small renal mass (SRM) varies significantly. The objective of this study was to determine which initial management strategy resulted in the greatest quality-adjusted life months (QALM) for an index patient with a SRM. METHODS: A Markov decision analysis was used to determine the effect of 1) treating patients with a partial nephrectomy (PN); 2) active surveillance (AS); and 3) renal mass biopsy on QALM over a 10-year horizon. All relevant health states were modelled. Biopsy sensitivity and specificity were modelled assuming an 80% prevalence of cancer using procedural pathology as the gold standard. Health state utilities were obtained from the Tufts Medical Centre Cost-Effective Analysis Registry. Deterministic sensitivity analyses were used to test key assumptions. RESULTS: Over a 10-year time horizon for a 70-year-old male with a 2 cm SRM, the biopsy strategy resulted in 38.07 QALM, whereas treating all patients with PN resulted in 37.69 QALM and AS in 36.25 QALM. The model was most sensitive to the probability that a patient would remain alive at baseline. Biopsy was the preferred strategy when sensitivity was greater than 77%. As the underlying probability of cancer increased, the threshold of renal mass biopsy sensitivity to still favor biopsy increased. CONCLUSIONS: Renal mass biopsy is the preferred initial management strategy for an index patient with a SRM to optimize QALM. When the probability of cancer is high, centers should aim for a sensitivity of at least 77% in order to consider a biopsy as the first strategy.

Predictors of Long-term Cardiovascular Versus Non-cardiovascular Mortality and Repeat Intervention in Patients Having Transcatheter Aortic Valve Implantation.

There is a paucity of literature characterizing the risk of long-term mortality and reintervention after transcatheter aortic valve implantation (TAVI). Addressing this gap has become increasingly relevant with the inclusion of intermediate and low surgical risk patients and the need for data to inform their long-term management. We sought to investigate the long-term trends and predictors of cardiovascular versus noncardiovascular mortality as well as reintervention in post-TAVI patients. Our cohort consisted of 5,406 patients who underwent TAVI in Ontario, Canada from 2011 to 2018. We used Kaplan-Meier analysis to estimate 7-year all-cause mortality and a Cox proportional hazard model to identify demographic, co-morbid, and procedural predictors. Similarly, cumulative incidence functions were used to estimate cardiovascular versus noncardiovascular mortality at 5 years, with predictors identified through Fine-Gray models. The Kaplan-Meier estimate for 7-year all-cause mortality in our cohort was 67%; this was driven by a number of co-morbidities including congestive heart failure and liver disease. We found that cardiovascular death was more likely for approximately the first 2 years post-TAVI whereas noncardiovascular death was more likely from this point to the end of the study. We identified a number of factors that uniquely modified the risk of either cardiovascular or noncardiovascular mortality. Only 1.6% of patients who underwent repeat intervention. The distinct factors associated with cardiovascular versus noncardiovascular death suggest different approaches to short-term and long-term surveillance of patients post-TAVI by both the heart team and primary care providers.

Trends in Utilization and Safety of In-Hospital Coronary Artery Bypass Grafting During a Non-ST-Segment Elevation Myocardial Infarction.

Up to 10% of non-ST-segment elevation myocardial infarction (NSTEMI) patients require coronary artery bypass graft (CABG) surgery during their hospitalization. Contemporary, real-world, data regarding CABG utilization and safety in NSTEMI patients are lacking. Our objectives were to investigate the contemporary trends in utilization and outcomes of CABG in patients admitted for NSTEMI. Using the 2003 to 2015 National Inpatient Sample data, we identified hospitalizations for NSTEMI, during which a CABG was performed. Patients' sociodemographic and clinical characteristics, incidence of surgical complications, length of stay, and mortality were analyzed. Multivariate analyses were performed to identify predictors of in-hospital complications and mortality. An estimated total of 440,371 CABG surgeries, during a hospitalization for NSTEMI, were analyzed. The utilization of CABG was steady over the years. The data show increasing prevalence of individual co-morbidities as well as cases with Deyo Co-morbidity Index ≥2 (p <0.001). High, 26.4%, complication rate was driven mainly by cardiac and pulmonary complications. The mortality rate declined from 3.6% in 2003 to an average of 2.4% during 2010 to 2015. Older age, female gender, heart failure, and delayed CABG timing were independent predictors of adverse outcomes. In conclusion, utilization of in-hospital CABG as the primary revascularization strategy in patients with NSTEMI remained steady over the years. These data reveal the raising prevalence of co-morbidities during the study. High complication rate was recorded; however, the mortality declined over the years to about 2.4%. Delaying CABG was associated with small but statistically significant worsening in outcomes.

Adjunctive laser-stimulated stem-cells therapy to primary reperfusion in acute myocardial infarction in humans: Safety and feasibility study.

BACKGROUND: Low-level laser therapy (LLLT) has photobiostimulatory effects on stem cells and may offer cardioprotection. This cell-based therapy may compliment primary percutaneous coronary intervention (PPCI) in patients with ST-segment elevation myocardial infarction (STEMI). OBJECTIVE: In this randomized control trial, our primary objective was to determine the safety and feasibility of LLLT application to the bone marrow in patients with STEMI undergoing PPCI. METHODS: We randomly assigned patients undergoing PPCI to LLLT or non-laser therapy (NLT). In the LLLT group, 100 s of laser therapy was applied to the tibia bone prior to PPCI, as well as 24 and 72 h post-PPCI. In the control group, the power source was turned off. The primary outcome was the difference in door-to-balloon (D2B) time, and additional outcomes included differences in circulating cell counts, cardiac enzymes, and left-ventricular ejection fraction (LVEF) at pre-specified intervals post-PPCI. RESULTS: Twenty-four patients were randomized to LLLT (N = 12) or NLT (N = 12). No adverse effects of the treatment were detected. The D2B time was not significantly different between the groups (41 ± 8 vs 48 ± 1 min; P = 0.73). Creatinine Phosphokinase area under the curve, was lower after LLLT (22 ± 10) compared to NLT (49 ± 12), but this was not statistically significant (P = 0.08). Troponin-T was significantly lower after LLLT (2.7 ± 1.4 ng/mL) in comparison to NLT (5.2 ± 1.8 ng/mL. P < 0.05). At 9 months, LVEF improved in both groups without a significant difference between LLLT (55 ± 9%) and NLT (52 ± 9%; P = 0.90). CONCLUSION: LLLT is a safe and feasible adjunctive cell-based therapy to PPCI that may benefit ischemic myocardium.

A mechanistic role for DNA methylation in endothelial cell (EC)-enriched gene expression: relationship with DNA replication timing.

Proximal promoter DNA methylation has been shown to be important for regulating gene expression. However, its relative contribution to the cell-specific expression of endothelial cell (EC)-enriched genes has not been defined. We used methyl-DNA immunoprecipitation and bisulfite conversion to analyze the DNA methylation profile of EC-enriched genes in ECs vs nonexpressing cell types, both in vitro and in vivo. We show that prototypic EC-enriched genes exhibit functional differential patterns of DNA methylation in proximal promoter regions of most (eg, CD31, von Willebrand factor [vWF], VE-cadherin, and intercellular adhesion molecule-2), but not all (eg, VEGFR-1 and VEGFR-2), EC-enriched genes. Comparable findings were evident in cultured ECs, human blood origin ECs, and murine aortic ECs. Promoter-reporter episomal transfection assays for endothelial nitric oxide synthase, VE-cadherin, and vWF indicated functional promoter activity in cell types where the native gene was not active. Inhibition of DNA methyltransferase activity indicated important functional relevance. Importantly, profiling DNA replication timing patterns indicated that EC-enriched gene promoters with differentially methylated regions replicate early in S-phase in both expressing and nonexpressing cell types. Collectively, these studies highlight the functional importance of promoter DNA methylation in controlling vascular EC gene expression.

Diagnosis of pericardial cysts using diffusion weighted magnetic resonance imaging: A case series.

INTRODUCTION: Congenital pericardial cysts are benign lesions that arise from the pericardium during embryonic development. The diagnosis is based on typical imaging features, but atypical locations and signal magnetic resonance imaging sequences make it difficult to exclude other lesions. Diffusion-weighted magnetic resonance imaging is a novel method that can be used to differentiate tissues based on their restriction to proton diffusion. Its use in differentiating pericardial cysts from other pericardial lesions has not yet been described. CASE PRESENTATION: We present three cases (a 51-year-old Caucasian woman, a 66-year-old Caucasian woman and a 77-year-old Caucasian woman) with pericardial cysts evaluated with diffusion-weighted imaging using cardiac magnetic resonance imaging. Each lesion demonstrated a high apparent diffusion coefficient similar to that of free water. CONCLUSION: This case series is the first attempt to investigate the utility of diffusion-weighted magnetic resonance imaging in the assessment of pericardial cysts. Diffusion-weighted imaging may be a useful noninvasive diagnostic tool for pericardial cysts when conventional imaging findings are inconclusive.