Iron deficiency in heart failure: getting to the guidelines.

PURPOSE OF REVIEW: Iron deficiency is a common condition affecting approximately 50% of patients with heart failure. The purpose of this review is to explore the impact of iron deficiency on patients' quality of life and outcomes. Moreover, how intravenous replacement, even in the absence of anemia, can improve these outcomes. RECENT FINDINGS: The role of iron deficiency anemia has long been a part of assessing reversible and treatable contributors to patients' symptoms in heart failure. Recent studies have demonstrated how vital identifying not only anemic patients but those who are iron deficient without anemia, may allow us to impact their quality of life by several different measures. The latter appears to be the case not only for reduced ejection fraction but also impacts patients with preserved ejection fraction who have very few other modalities which improve symptoms. SUMMARY: Iron deficiency in heart failure is common, and with improvements in diagnosis and management, it has led to a better understanding of the importance of iron deficiency in cardiac failure and function.

Intravascular imaging in the diagnosis and management of patients with suspected intracoronary pathologies: A CJC White Paper.

Intravascular imaging has become an integral part of the diagnostic and management strategies for intracoronary pathologies. This White Paper summarizes current evidence and its implications on the use of intravascular imaging in interventional cardiology practice. The areas addressed are planning and optimization of percutaneous coronary intervention, management of stent failure, and evaluation of ambiguous coronary lesions and myocardial infarction with non-obstructive coronary disease (MINOCA). Findings are presented following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system in an expert consensus process involving a diverse Writing group and vetted by a Review group. Expert consensus was achieved around nine statements. Use of intravascular imaging in guiding percutaneous revascularization is supported by high quality evidence, particularly for lesions with increased risk of recurrent events or stent failure. Specific considerations for intravascular imaging guidance of intervention in left main lesions, chronic occlusion lesions as well as patients at high risk of contrast nephropathy are explored. Use of intravascular imaging to identify pathologies associated with stent failure and guide repeat intervention, resolve ambiguities in lesion assessment and establish diagnoses in patients presenting with MINOCA is supported by moderate to low quality evidence. Each topic is accompanied by clinical pointers to aid the practicing interventional cardiologist in implementation of the White paper findings. The findings of this White Paper will help to guide the utilization of intravascular imaging towards those situations in which the balance of efficacy, safety and cost are most optimal.

Catheter-Induced Postextrasystolic Potentiation in the Assessment of Severity of Low-Gradient Aortic Valve Stenosis.

BACKGROUND: Deciphering which patients with low-gradient aortic valve disease have severe stenosis can be difficult. We aimed to correlate the postextrasystolic potentiation (PESP) with dobutamine stress echocardiography and multidetector computed tomography in patients with low-gradient aortic valve stenosis. METHODS: Patients with an aortic valve area ≤1 cm2 and a mean gradient <40 mm Hg were included. Aortic valve stenosis severity was assessed by a core lab with dobutamine stress echocardiography, followed by a multidetector computed tomography aortic valve score if indeterminate. A premature ventricular contraction was induced by intentional catheter contact with the myocardium within the left ventricle. PESP was calculated as a percent change of pre-to-post mean gradient. Multidetector computed tomography was used to measure the aortic valve calcification score, and subsequently, aortic valve calcification density. RESULTS: Twenty-eight patients (age, 77±10 years; 19 female) were included. Dobutamine stress echocardiography increased mean gradient from baseline of 25±7 mm Hg to 36±11 mm Hg; pre-premature ventricular contraction mean gradient was 25±7 mm Hg and increased to post-premature ventricular contraction mean gradient of 32±10 mm Hg, representing a PESP of 24±11%. A ≥20% in PESP resulted in 100% sensitivity, 77% specificity, 83% positive predictive value, and 100% negative predictive value for diagnosing severe aortic valve stenosis. There was a significant correlation between PESP and projected aortic valve area and aortic valve calcification density (R=-0.64, P=0.0003; R=0.057, P=0.014, respectively). CONCLUSIONS: In patients with low-gradient aortic valve stenosis, catheter-induced premature ventricular contractions during cardiac catheterization causing ≥20% PESP has a 100% sensitivity for severe aortic valve stenosis. Validation of this 20% cutoff in larger groups with correlation to clinical end points is required.

Antithrombotic therapies in Canadian atrial fibrillation patients with concomitant coronary artery disease: Insights from the CONNECT AF + PCI-II program.

BACKGROUND: Selecting the appropriate antithrombotic regimen for patients with atrial fibrillation (AF) who have undergone percutaneous coronary intervention (PCI) or have had medically managed acute coronary syndrome (ACS) remains complex. This multi-centre observational study evaluated patterns of antithrombotic therapies utilized among Canadian patients with AF post-PCI or ACS. METHODS AND RESULTS: By retrospective chart audit, 611 non-valvular AF patients [median (interquartile range) age 76 (69-83) years, CHADS2 score 2 (1-3)] who underwent PCI or had medically managed ACS between August 2018 and December 2020 were identified by 68 cardiologists across eight provinces in Canada. Overall, triple antithrombotic therapy [TAT: combined oral anticoagulation (OAC) and dual antiplatelet therapy (DAPT)] was the most common initial antithrombotic strategy, with use in 53.8 % of patients, followed by dual pathway therapy (32.7 % received OAC and a P2Y12 inhibitor, and 4.1 % received OAC and aspirin) and DAPT (9.3 %). Median duration of TAT was 30 (7, 30) days. Compared to the previous CONNECT AF + PCI-I program, there was an increased use of dual pathway therapy relative to TAT over time (P-value <.0001). DOACs (direct oral anticoagulants) represented 90.3 % of all OACs used overall, with apixaban being the most utilized (50.5 %). Proton pump inhibitors were used in 57.0 % of all patients, and 70.1 % of patients on ASA. Planned antithrombotic therapies at 1 year were: 76.2 % OAC monotherapy, 8.3 % OAC + ASA, 7.9 % OAC + P2Y12 inhibitor, 4.3 % DAPT, 1.3 % ASA alone, and <1 % triple therapy. CONCLUSION: In accordance with recent Canadian Cardiovascular Society guideline recommendations, we observed an increased use of dual pathway therapy relative to TAT over time in both AF patients post-PCI (elective and emergent) and in those with medically managed ACS. Additionally, DOACs have become the prevailing form of anticoagulation across all antithrombotic regimens. Our findings suggest that Canadian physicians are integrating evidence-based approaches to optimally manage the bleeding and thrombotic risks of AF patients post-PCI and/or ACS.

Cardiac impairments in postacute COVID-19 with sustained symptoms: A review of the literature and proof of concept.

Although acute COVID-19 is known to cause cardiac damage in some cases, there is still much to learn about the duration and relative permanence of the damage that may occur. Long COVID is a condition that can occur when COVID-19 symptoms remain in the postviral acute period. Varying accounts of long COVID have been described across the literature, however, cardiac impairments are sustained in many individuals and cardiovascular assessment is now considered to be an expected follow-up examination. The purpose of this review and proof of concept is to summarize the current research related to the assessment of cardiac function, including echocardiography and blood biomarker data, during the follow-up period in patients who recovered from COVID-19. Following a literature review, it was found that right ventricular dysfunction along with global longitudinal strain and diastolic dysfunction are common findings. Finally, more severe acute myocardial injury during the index hospitalization appears to exacerbate cardiac function. The available literature implies that cardiac function must be monitored in patients recovered from COVID-19 who remain symptomatic and that the impairments and severity vary from person-to-person. The proof-of-concept analysis of patients with cardiac disease and respiratory disease in comparison to those with sustained symptoms from COVID-19 suggests elevated systolic time interval in those with sustained symptoms from COVID-19, thus reducing heart performance indices. Future research must consider the details of cardiac complications during the acute infection period and relate this to the cardiac function in patients with long COVID during mid- and long-term follow-up.

Novel effects of acute COVID-19 on cardiac mechanical function: Two case studies.

The spread of the novel coronavirus 2019 (COVID-19) has caused a global pandemic. The disease has spread rapidly, and research shows that COVID-19 can induce long-lasting cardiac damage. COVID-19 can result in elevated cardiac biomarkers indicative of acute cardiac injury, and research utilizing echocardiography has shown that there is mechanical dysfunction in these patients as well, especially when observing the isovolumic, systolic, and diastolic portions of the cardiac cycle. The purpose of this study was to present two case studies on COVID-19 positive patients who had their cardiac mechanical function assessed every day during the acute period to show that cardiac function in these patients was altered, and the damage occurring can change from day-to-day. Participant 1 showed compromised cardiac function in the systolic time, diastolic time, isovolumic time, and the calculated heart performance index (HPI), and these impairments were sustained even 23 days post-symptom onset. Furthermore, Participant 1 showed prolonged systolic periods that lasted longer than the diastolic periods, indicative of elevated pulmonary artery pressure. Participant 2 showed decreases in systole and consequently, increases in HPI during the 3 days post-symptom onset, and these changes returned to normal after day 4. These results showed that daily observation of cardiac function can provide detailed information about the overall mechanism by which cardiac dysfunction is occurring and that COVID-19 can induce cardiac damage in unique patterns and thus can be studied on a case-by-case basis, day-to-day during infection. This could allow us to move toward more personalized cardiovascular medical treatment.

Provision of a DAPT Score to Cardiologists and Extension of Dual Antiplatelet Therapy Beyond 1 Year After ACS: Randomized Substudy of the Prospective Canadian ACS Reflective II Study.

BACKGROUND: Extension of dual antiplatelet therapy (DAPT) beyond 1 year after acute coronary syndrome is associated with a reduction in ischemic events but also increased bleeding. The DAPT score identifies individuals likely to derive overall benefit or harm from DAPT extension. We sought to evaluate the impact of providing the DAPT score to treating physicians on the decision to extend DAPT beyond 1 year after non-ST-segment elevation myocardial infarction. METHODS: Moderate to high-risk non-ST-segment elevation myocardial infarction patients were enrolled from July 2016 to May 2018 in 13 Canadian hospitals by 52 cardiologists. Participating cardiologists were randomly assigned 1:1 to receive their individual patients' DAPT scores before the 1-year follow-up visit vs not receiving their patients' DAPT scores. Rates of DAPT extension were compared among the randomized groups. RESULTS: At 1 year, 370 of the 585 (63.2%) patients discharged on DAPT were receiving DAPT. Among patients on DAPT at 1 year, the median (25th, 75th percentile) DAPT score was 2 (1,3). DAPT was extended beyond 1 year in 36.2% randomly assigned to provision of DAPT score vs 35.7% in the control group (P = 0.93). In the subgroup of patients with DAPT score ≥ 2, DAPT extension was 49.5% in the DAPT score provision arm vs 40.4% in the control arm (P = 0.22); among patients with DAPT score < 2, DAPT termination was 78.6% in the DAPT score provision arm vs 70.6% in the control arm (P = 0.26) (P value for interaction = 0.1). CONCLUSIONS: In this exploratory randomized trial, provision of the DAPT score to treating physicians had no impact on the duration of DAPT treatment beyond 1 year.

INTRODUCTION: La prolongation de la bithérapie antiplaquettaire au-delà d'un an après un syndrome coronarien aigu est associée à la réduction des accidents ischémiques, mais aussi à l'augmentation des hémorragies. Le score de bithérapie antiplaquettaire permet de déterminer les individus susceptibles d'obtenir des avantages globaux ou des inconvénients de la prolongation de la bithérapie antiplaquettaire. Nous avons cherché à évaluer les répercussions de l'obtention du score de bithérapie antiplaquettaire par les médecins traitants sur la décision quant à la prolongation de la bithérapie antiplaquettaire au-delà d'un an après l'infarctus du myocarde sans élévation du segment ST. MÉTHODES: De juillet 2016 à mai 2018, 52 cardiologues de 13 hôpitaux du Canada ont inscrit des patients exposés à un risque modéré à élevé d'infarctus du myocarde sans élévation du segment ST. Nous avons réparti de façon aléatoire selon un rapport 1:1 les cardiologues participants qui recevaient les scores de bithérapie antiplaquettaire individuels de leurs patients avant la consultation de suivi après un an vs ceux qui ne recevaient pas les scores de bithérapie antiplaquettaire de leurs patients. Nous avons comparé les taux de prolongation de la bithérapie antiplaquettaire des groupes répartis de façon aléatoire. RÉSULTATS: Après un an, 370 (63,2 %) patients sur 585 qui avaient eu à la sortie de l'hôpital une bithérapie antiplaquettaire recevaient la bithérapie antiplaquettaire. Parmi les patients qui prenaient la bithérapie antiplaquettaire après un an, le score médian de bithérapie antiplaquettaire (25e, 75e percentiles) était de 2 (1, 3). La bithérapie antiplaquettaire était prolongée au-delà d'un an chez 36,2 % des patients répartis de façon aléatoire qui avaient un score de bithérapie antiplaquettaire vs 35,7 % dans le groupe témoin (P = 0,93). Dans le sous-groupe de patients qui avaient un score de bithérapie antiplaquettaire ≥ 2, la prolongation de la bithérapie antiplaquettaire était de 49,5 % dans le bras qui avait un score de bithérapie antiplaquettaire vs 40,4 % dans le bras témoin (P = 0,22); parmi les patients qui avaient un score de bithérapie antiplaquettaire < 2, la cessation de la bithérapie antiplaquettaire était de 78,6 % dans le bras qui avait un score de bithérapie antiplaquettaire vs 70,6 % dans le bras témoin (P = 0,26) (valeur P pour l'interaction = 0,1). CONCLUSIONS: Dans cet essai exploratoire à répartition aléatoire, l'obtention du score de la bithérapie antiplaquettaire par les médecins traitants n'a pas engendré de répercussions sur la durée de la bithérapie antiplaquettaire au-delà d'un an.

Contemporary use of guideline-based higher potency P2Y12 receptor inhibitor therapy in patients with moderate-to-high risk non-ST-segment elevation myocardial infarction: Results from the Canadian ACS reflective II cross-sectional study.

BACKGROUND: After myocardial infarction, guidelines recommend higher-potency P2Y12 receptor inhibitors, namely ticagrelor and prasugrel, over clopidogrel. HYPOTHESIS: We aimed to determine the contemporary use of higher-potency antiplatelet therapy in Canadian patients with non-ST-elevation myocardial infarction (NSTEMI). METHODS: A total of 684 moderate-to-high risk NSTEMI patients were enrolled in the prospective Canadian ACS Reflective II registry at 12 Canadian hospitals and three clinics in five provinces between July 2016 and May 2018. Multivariable logistic regression modeling was performed to assess factors independently associated with higher-potency P2Y12 receptor inhibitor use at discharge. RESULTS: At hospital discharge, 78.3% of patients were treated with a P2Y12 receptor inhibitor. Among patients discharged on a P2Y12 receptor inhibitor, use of higher-potency P2Y12 receptor inhibitor was 61.4%. After adjustment, treatment in-hospital with PCI (OR 4.48, 95%CI 3.34-6.03, p < .0001) was most strongly associated with higher use of higher-potency P2Y12 receptor inhibitor, while oral anticoagulant use at discharge (OR 0.03, 95%CI 0.01-0.12, p < .0001), and atrial fibrillation (OR 0.40, 95%CI 0.17-0.98, p = .046) were most strongly associated with lower use of higher-potency P2Y12 receptor inhibitor. Use of higher-potency P2Y12 receptor inhibitor varied across provinces (range, 21.6%-78.9%). DISCUSSION: In contemporary Canadian practice, approximately 60% of moderate-to-high risk NSTEMI patients discharged on a P2Y12 receptor inhibitor are treated with a higher-potency P2Y12 receptor inhibitor. In addition to factors that increase risk of bleeding, interprovincial differences in practice patterns were associated with use of higher-potency P2Y12 receptor inhibitor at discharge. Opportunities remain for further optimization of evidence-based, guideline-recommended antiplatelet therapy use.

Southern Saskatchewan Ticagrelor Registry experience.

BACKGROUND: As ticagrelor enters into clinical use for acute coronary syndrome, it is important to understand patient/physician behavior in terms of appropriate use, adherence, and event rates. METHODS: The Southern Saskatchewan Ticagrelor Registry is a prospective, observational, multicenter cohort study that identifies consecutive patients started on ticagrelor. We aimed to evaluate both on- and off-label use, identify characteristics of patients who prematurely stop ticagrelor, and describe patient/physician behavior contributing to inappropriate stoppage of this medication. RESULTS: From April 2012 to September 2013, 227 patients were initiated on ticagrelor, with a mean age of 62.2±12.1 years. The participants were 66% men and had a mean follow up of 157.4±111.7 days. Seventy-four patients (32.4%) had off-label indications. Forty-seven patients (20.7%) prematurely stopped ticagrelor and were more likely to be older, women, nonwhite, present with shock, and complain of dyspnea. Twenty-six of the 47 patients stopped ticagrelor inappropriately because of patient nonadherence (18 patients) and physician advice (eight patients). A composite outcome event of death from vascular causes, myocardial infarction, or stroke occurred in 8.8% of the entire cohort and was more likely to occur in those older then 65 years, those presenting with cardiogenic shock, and those who prematurely stopped ticagrelor. CONCLUSION: In this real-world registry of patients started on ticagrelor, a third have off-label indications and a fifth prematurely stop the medication. Premature discontinuation was an independent predictor of major life-threatening bleeding and increased composite event rate of death from vascular causes, myocardial infarction, or stroke.

Plaque progression in coronary arteries with minimal luminal obstruction in intravascular ultrasound atherosclerosis trials.

The relation among the burden of disease, progression of atherosclerosis, and remodeling in angiographically minimally diseased coronary arteries has not been defined. The present analysis included 1,906 patients who participated in 5 prospective clinical trials examining atheroma progression using intravascular ultrasonography. For the present analysis, the patients were stratified according to baseline quantitative coronary angiographic stenosis: <20%, 20% to 35%, and >35%. Patients with a lesser degree of luminal stenosis had less atherosclerosis. However, in the arteries with minimal angiographic stenosis, a large percentage of images contained atheroma, demonstrating the diffuse nature of coronary atherosclerosis. All 3 groups showed evidence of disease progression. The serial changes in vessel dimensions revealed that both the external elastic membrane and lumen volumes decreased in all 3 subgroups, in keeping with vessel and luminal constriction. In conclusion, these findings have demonstrated that patients with at least one luminal stenosis have diffuse atherosclerosis that progressed during 18 to 24 months, making them a target for therapeutic intervention. These minimally diseased arteries demonstrated evidence of vessel and luminal constriction, regardless of the angiographic appearance.

Comparison of rates of progression of coronary atherosclerosis in patients with diabetes mellitus versus those with the metabolic syndrome.

Diabetes mellitus (DM) and metabolic syndrome (MS) are associated with adverse cardiovascular outcomes. However, the extent and progression of coronary atherosclerosis for these conditions have not been directly compared. Three thousand four hundred fifty-nine patients with coronary artery disease underwent serial evaluation of atheroma burden by intravascular ultrasound. Patients with DM, MS, or neither diagnosis were compared with regard to plaque burden, progression, and arterial remodeling. Among the 3 groups, patients with MS had the largest number of individual cardiovascular risk factors. Patients with DM demonstrated more extensive atherosclerosis burden with a greater percent atheroma volume compared to patients with MS or those with neither diagnosis (40.3 +/- 9.0%, 37.6 +/- 8.9%, and 38.1 +/- 9.1%, p <0.001) and total atheroma volume (198.3 +/- 85.9, 190.7 +/- 85.0, and 186.3 +/- 79.1 mm(3), p = 0.05). MS compared to neither diagnosis was accompanied by expansion of the external elastic membrane (501.3 +/- 174.3 vs 484.4 +/- 160.7 mm(3), p = 0.02), whereas DM was associated with lumen constriction (290.6 +/- 111.7 vs 298.1 +/- 105.5 mm(3), p <0.0001). On serial evaluation, DM, but not MS, was associated with greater progression of percent atheroma volume compared to neither diagnosis (+0.8 +/- 0.3, +0.3 +/- 0.2, and +0.1 +/- 0.2%, p <0.0001) and total atheroma volume (-1.0 +/- 1.8, -3.3 +/- 1.8, and -4.0 +/- 1.8 mm(3), p = 0.001). Meeting criteria for MS was not associated with greater disease progression in patients with DM. In conclusion, despite having fewer individual risk factors, DM is associated with greater plaque progression and more constrictive remodeling than MS. This finding highlights the deleterious effects of DM on the arterial wall independent of its associated metabolic abnormalities.

Clinical predictors of plaque progression despite very low levels of low-density lipoprotein cholesterol.

OBJECTIVES: The purpose of this study was to characterize the determinants of plaque progression despite achieving very low levels of low-density lipoprotein cholesterol (LDL-C). BACKGROUND: Despite achieving very low levels of LDL-C, many patients continue to demonstrate disease progression and have clinical events. METHODS: A total of 3,437 patients with coronary artery disease underwent serial intravascular ultrasound examination in 7 clinical trials. Patients who achieved an on-treatment LDL-C level of 20% of patients continued to progress. There were no demographic differences between groups. Progressors demonstrated higher baseline levels of glucose (117.1 +/- 42.5 mg/dl vs. 112.1 +/- 40.0 mg/dl, p = 0.02), triglycerides (157.5 mg/dl vs. 133.0 mg/dl, p = 0.004), and a smaller decrease of apolipoprotein B (-25.1 +/- 3.4 mg/dl vs. -27.4 +/- 3.35 mg/dl, p = 0.01) at follow-up. Multivariable analysis revealed that independently associated risk factors of progression in patients with LDL-C