Fractional Flow Reserve-Guided PCI as Compared with Coronary Bypass Surgery.

BACKGROUND: Patients with three-vessel coronary artery disease have been found to have better outcomes with coronary-artery bypass grafting (CABG) than with percutaneous coronary intervention (PCI), but studies in which PCI is guided by measurement of fractional flow reserve (FFR) have been lacking. METHODS: In this multicenter, international, noninferiority trial, patients with three-vessel coronary artery disease were randomly assigned to undergo CABG or FFR-guided PCI with current-generation zotarolimus-eluting stents. The primary end point was the occurrence within 1 year of a major adverse cardiac or cerebrovascular event, defined as death from any cause, myocardial infarction, stroke, or repeat revascularization. Noninferiority of FFR-guided PCI to CABG was prespecified as an upper boundary of less than 1.65 for the 95% confidence interval of the hazard ratio. Secondary end points included a composite of death, myocardial infarction, or stroke; safety was also assessed. RESULTS: A total of 1500 patients underwent randomization at 48 centers. Patients assigned to undergo PCI received a mean (±SD) of 3.7±1.9 stents, and those assigned to undergo CABG received 3.4±1.0 distal anastomoses. The 1-year incidence of the composite primary end point was 10.6% among patients randomly assigned to undergo FFR-guided PCI and 6.9% among those assigned to undergo CABG (hazard ratio, 1.5; 95% confidence interval [CI], 1.1 to 2.2), findings that were not consistent with noninferiority of FFR-guided PCI (P = 0.35 for noninferiority). The incidence of death, myocardial infarction, or stroke was 7.3% in the FFR-guided PCI group and 5.2% in the CABG group (hazard ratio, 1.4; 95% CI, 0.9 to 2.1). The incidences of major bleeding, arrhythmia, and acute kidney injury were higher in the CABG group than in the FFR-guided PCI group. CONCLUSIONS: In patients with three-vessel coronary artery disease, FFR-guided PCI was not found to be noninferior to CABG with respect to the incidence of a composite of death, myocardial infarction, stroke, or repeat revascularization at 1 year. (Funded by Medtronic and Abbott Vascular; FAME 3 ClinicalTrials.gov number, NCT02100722.).

Fractional Flow Reserve-Guided PCI or Coronary Bypass Surgery for 3-Vessel Coronary Artery Disease: 3-Year Follow-Up of the FAME 3 Trial.

BACKGROUND: Previous studies comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel coronary disease not involving the left main have shown significantly lower rates of death, myocardial infarction (MI), or stroke after CABG. These studies did not routinely use current-generation drug-eluting stents or fractional flow reserve (FFR) to guide PCI. METHODS: FAME 3 (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) is an investigator-initiated, multicenter, international, randomized trial involving patients with 3-vessel coronary artery disease (not involving the left main coronary artery) in 48 centers worldwide. Patients were randomly assigned to receive FFR-guided PCI using zotarolimus drug-eluting stents or CABG. The prespecified key secondary end point of the trial reported here is the 3-year incidence of the composite of death, MI, or stroke. RESULTS: A total of 1500 patients were randomized to FFR-guided PCI or CABG. Follow-up was achieved in >96% of patients in both groups. There was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI compared with CABG (12.0% versus 9.2%; hazard ratio [HR], 1.3 [95% CI, 0.98-1.83]; P=0.07). The rates of death (4.1% versus 3.9%; HR, 1.0 [95% CI, 0.6-1.7]; P=0.88) and stroke (1.6% versus 2.0%; HR, 0.8 [95% CI, 0.4-1.7]; P=0.56) were not different. MI occurred more frequently after PCI (7.0% versus 4.2%; HR, 1.7 [95% CI, 1.1-2.7]; P=0.02). CONCLUSIONS: At 3-year follow-up, there was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI with current-generation drug-eluting stents compared with CABG. There was a higher incidence of MI after PCI compared with CABG, with no difference in death or stroke. These results provide contemporary data to allow improved shared decision-making between physicians and patients with 3-vessel coronary artery disease. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02100722.

Comparison of Immune Profiles in Fetal Hearts with Idiopathic Dilated Cardiomyopathy, Maternal Autoimmune-Associated Dilated Cardiomyopathy and the Normal Fetus.

The etiology of idiopathic dilated cardiomyopathy (iDCM) remains unknown. Immune therapies have improved outcome in fetuses with DCM born to mothers with autoimmune disease (aDCM). The purpose of this retrospective study was to compare the myocardial B and T cell profiles in fetuses and neonates with idiopathic DCM (iDCM) versus autoimmune-mediated DCM (aDCM) and to describe the normal cell maturation within the human fetal myocardium. Of 60 fetal autopsy cases identified from institutional databases, 10 had aDCM (18-38 weeks), 12 iDCM (19-37 weeks) and 38 had normal hearts (11-40 weeks). Paraffin-embedded myocardium sections were stained for all lymphocyte (CD45), B cells (CD20, CD79a), T cells (CD3, CD4, CD7, CD8) and monocyte (CD68) surface markers. Two independent, blinded cell counts were performed. Normal hearts expressed all B and T cell markers in a bimodal fashion, with peaks at 22 and 37 weeks of gestation. The aDCM cohort was most distinct from normal hearts, with less overall T cell markers [EST -9.1 (2.6) cells/mm(2), p = 0.001], CD4 [EST -2.0 (0.6), p = 0.001], CD3 [EST -3.9 (1.0), p < 0.001], CD7 [EST -3.0 (1.1), p = 0.01] overall B cell markers [EST -4.9 (1.8), p = 0.01] and CD79a counts [EST -2.3 (0.9), p = 0.01]. The iDCM group had less overall B cell markers [EST -4.0 (1.8), p = 0.03] and CD79a [EST -1.7 (0.9), p = 0.05], but no difference in T cell markers. Autoimmune-mediated DCM fetuses have less B and T cell markers, whereas iDCM fetuses have less B cell markers compared with normal fetal hearts. The fetal immune system may play a role in the normal development of the heart and evolution of dilated cardiomyopathy.

Factors associated with in utero demise of fetuses that have underlying cardiac pathologies.

Factors associated with in utero fetal demise (IUFD) of fetuses that have underlying cardiac pathologies are largely unknown. This case-control study aimed to define the prevalence of IUFD in fetuses with a diagnosis of cardiac pathologies and to identify prenatal predictors of IUFD. Between January 2004 and December 2010, 74 IUFD cases [4.6 %; 95 % confidence interval (CI) 3.7-5.8 %] were identified from 1,584 cases with a diagnosis of structural or functional cardiac lesions in the Hospital for Sick Children database. The cases were divided into right-sided (N = 28), left-sided (N = 23), great artery (N = 8), and miscellaneous (N = 15) groups. The control subjects (1:1 ratio) were fetuses that had cardiac pathology diagnosed within 48 h of the IUFD case. Multivariable regression models were used to determine echocardiographic predictors of IUFD. The prevalence of IUFD was greatest in hypertrophic cardiomyopathy (8/16, 50 %) and Ebstein's anomaly/tricuspid dysplasia (4/15, 27 %) and lowest in transposition of the great arteries (2/85, 1 %). The findings showed IUFD to be associated with hydrops in 17 (23 %) of the 74 cases and arrhythmia in 11 (15 %) of the 74 cases. The factors identified by univariable logistic regression analyses were right ventricular dysfunction [odds ratio (OR) 2.7; p = 0.001], left ventricular dysfunction (OR 1.8; p = 0.007), umbilical vein pulsations (OR 10.9; p = 0.002), and abnormal ductus venosus flow (OR 3.3; p = 0.01). The factors associated with IUFD in multivariable logistic regression models were cardiomegaly (OR 5.6; p = 0.01), hydrops (OR 29.5; p = 0.001), pericardial effusion (OR 4.1; p = 0.06), and extracardiac abnormalities (OR 7.2; p < 0.001). The prevalence of IUFD is greatest in conditions affecting the ventricular myocardium. The onset of IUFD appears to be related initially to right ventricular dysfunction. Closer surveillance is recommended for lesions at risk of IUFD.

Angiographic Coronary Slow Flow Is Not a Valid Surrogate for Invasively Diagnosed Coronary Microvascular Dysfunction.

BACKGROUND: Ischemia with no obstructive coronary arteries is frequently caused by coronary microvascular dysfunction (CMD). Consensus diagnostic criteria for CMD include baseline angiographic slow flow by corrected TIMI (Thrombolysis In Myocardial Infarction) frame count (cTFC), but correlations between slow flow and CMD measured by invasive coronary function testing (CFT) are uncertain. OBJECTIVES: The aim of this study was to investigate relationships between cTFC and invasive CFT for CMD. METHODS: Adults with ischemia with no obstructive coronary arteries underwent invasive CFT with thermodilution-derived baseline coronary blood flow, coronary flow reserve (CFR), and index of microcirculatory resistance (IMR). CMD was defined as abnormal CFR (<2.5) and/or abnormal IMR (≥25). cTFC was measured from baseline angiography; slow flow was defined as cTFC >25. Correlations between cTFC and baseline coronary flow and between CFR and IMR and associations between slow flow and invasive measures of CMD were evaluated, adjusted for covariates. All patients provided consent. RESULTS: Among 508 adults, 49% had coronary slow flow. Patients with slow flow were more likely to have abnormal IMR (36% vs 26%; P = 0.019) but less likely to have abnormal CFR (28% vs 42%; P = 0.001), with no difference in CMD (46% vs 51%). cTFC was weakly correlated with baseline coronary blood flow (r = -0.35; 95% CI: -0.42 to -0.27), CFR (r = 0.20; 95% CI: 0.12 to 0.28), and IMR (r = 0.16; 95% CI: 0.07-0.24). In multivariable models, slow flow was associated with lower odds of abnormal CFR (adjusted OR: 0.53; 95% CI: 0.35 to 0.80). CONCLUSIONS: Coronary slow flow was weakly associated with results of invasive CFT and should not be used as a surrogate for the invasive diagnosis of CMD.

The relationships between acetylcholine-induced chest pain, objective measures of coronary vascular function and symptom status.

Background: Acetylcholine-induced chest pain is routinely measured during the assessment of microvascular function. Aims: The aim was to determine the relationships between acetylcholine-induced chest pain and both symptom burden and objective measures of vascular function. Methods: In patients with angina but no obstructive coronary artery disease, invasive studies determined the presence or absence of chest pain during both acetylcholine and adenosine infusion. Thermodilution-derived coronary blood flow (CBF) and index of microvascular resistance (IMR) was determined at rest and during both acetylcholine and adenosine infusion. Patients with epicardial spasm (>90%) were excluded; vasoconstriction between 20% and 90% was considered endothelial dysfunction. Results: Eighty-seven patients met the inclusion criteria. Of these 52 patients (60%) experienced chest pain during acetylcholine while 35 (40%) did not. Those with acetylcholine-induced chest pain demonstrated: (1) Increased CBF at rest (1.6 ± 0.7 vs. 1.2 ± 0.4, p = 0.004) (2) Decreased IMR with acetylcholine (acetylcholine-IMR = 29.7 ± 16.3 vs. 40.4 ± 17.1, p = 0.004), (3) Equivalent IMR following adenosine (Adenosine-IMR: 21.1 ± 10.7 vs. 21.8 ± 8.2, p = 0.76), (4) Increased adenosine-induced chest pain (40/52 = 77% vs. 7/35 = 20%, p < 0.0001), (5) Increased chest pain during exercise testing (30/46 = 63% vs. 4/29 = 12%, p < 0.00001) with no differences in exercise duration or electrocardiographic changes, and (6) Increased prevalence of epicardial endothelial dysfunction (33/52 = 63% vs. 14/35 = 40%, p = 0.03). Conclusions: After excluding epicardial spasm, acetylcholine-induced chest pain is associated with increased pain during exercise and adenosine infusion, increased coronary blood flow at rest, decreased microvascular resistance in response to acetylcholine and increased prevalence of epicardial endothelial dysfunction. These findings raise questions about the mechanisms underlying acetylcholine-induced chest pain.

Comprehensive Management of ANOCA, Part 1-Definition, Patient Population, and Diagnosis: JACC State-of-the-Art Review.

Angina with nonobstructive coronary arteries (ANOCA) is increasingly recognized and may affect nearly one-half of patients undergoing invasive coronary angiography for suspected ischemic heart disease. This working diagnosis encompasses coronary microvascular dysfunction, microvascular and epicardial spasm, myocardial bridging, and other occult coronary abnormalities. Patients with ANOCA often face a high burden of symptoms and may experience repeated presentations to multiple medical providers before receiving a diagnosis. Given the challenges of establishing a diagnosis, patients with ANOCA frequently experience invalidation and recidivism, possibly leading to anxiety and depression. Advances in scientific knowledge and diagnostic testing now allow for routine evaluation of ANOCA noninvasively and in the cardiac catheterization laboratory with coronary function testing (CFT). CFT includes diagnostic coronary angiography, assessment of coronary flow reserve and microcirculatory resistance, provocative testing for endothelial dysfunction and coronary vasospasm, and intravascular imaging for identification of myocardial bridging, with hemodynamic assessment as needed.

Comprehensive Management of ANOCA, Part 2-Program Development, Treatment, and Research Initiatives: JACC State-of-the-Art Review.

Centers specializing in coronary function testing are critical to ensure a systematic approach to the diagnosis and treatment of angina with nonobstructive coronary arteries (ANOCA). Management leveraging lifestyle, pharmacology, and device-based therapeutic options for ANOCA can improve angina burden and quality of life in affected patients. Multidisciplinary care teams that can tailor and titrate therapies based on individual patient needs are critical to the success of comprehensive programs. As coronary function testing for ANOCA is more widely adopted, collaborative research initiatives will be fundamental to improve ANOCA care. These efforts will require standardized symptom assessments and data collection, which will propel future large-scale clinical trials.

Concurrently Low Coronary Flow Reserve and Low Index of Microvascular Resistance Are Associated With Elevated Resting Coronary Flow in Patients With Chest Pain and Nonobstructive Coronary Arteries.

BACKGROUND: Coronary microvascular function can be distinctly quantified using the coronary flow reserve (CFR) and index of microvascular resistance (IMR). Patients with low CFR can present with low or high IMR, although the prevalence and clinical characteristics of these patient groups remain unclear. METHODS: One hundred ninety-nine patients underwent coronary microvascular assessments using coronary thermodilution techniques. A pressure-temperature sensor-tipped guidewire measured proximal and distal coronary pressure, whereas the inverse of the mean transit time to room temperature saline was used to measure coronary blood flow. The CFR and IMR were quantified during adenosine and acetylcholine hyperemia. RESULTS: Low adenosine and acetylcholine CFR was observed in 70 and 49 patients, respectively, whereas low CFR/low IMR to adenosine and acetylcholine was observed in 39(56%) and 19(39%) patients, respectively. Despite similar adenosine CFR, patients with low CFR/low IMR had increased resting (2.8±1.2 versus 1.3±0.4s-1) and hyperemic coronary blood flow (4.8±1.5 versus 2.1±0.5s-1) compared with patients with low CFR/high IMR (both P<0.01). The same pattern was observed in response to acetylcholine. Patients with low CFR/low IMR to adenosine were younger (56±12 versus 63±10 years), women (84% versus 66%), had fewer coronary risk factors (1.1±1.0 versus 1.6±1.1), lower hemoglobin A1c (5.8±0.7 versus 6.1±0.9 mmol/L), and thinner septal thickness (8.5±2.5 versus 9.9±1.6 mm) compared with patients with low CFR/high IMR to adenosine (all P<0.05). CONCLUSIONS: Low CFR/low IMR to adenosine and acetylcholine are associated with elevated resting coronary blood flow and preserved hyperemic coronary blood flow. These patients present with distinct phenotypic characteristics. Simultaneous CFR and IMR measures appear necessary to differentiate these endotypes.

Prospective Assessment of Coronary Artery Flows Before and After Cardiopulmonary Bypass in Children With a Spectrum of Congenital Heart Disease.

Background: Normative data for the effect of cardiopulmonary bypass (CPB) on coronary artery Doppler velocities by transesophageal echocardiography in paediatric patients with congenital heart disease (CHD) are lacking. The objective of the study was to prospectively examine the effects of CPB on coronary artery flow patterns by transesophageal echocardiography before and after CPB in children with CHD. Methods: All cases undergoing CHD surgery at the Hospital for Sick Children, Toronto, were eligible. The excluded cases included Norwood operation, heart transplantation, or weight <2.5 kg. Coronary Dopplers and coronary flow reserve (CFR) for the right coronary artery (RCA) and left anterior descending (LAD) were obtained. Multivariable analyses using linear regression models were performed, adjusted for age and cross-clamp time. Results: From May 2017 to June 2018, 69 children (median age at surgery: 0.7 years, interquartile range [IQR]: 0.4-3.7 years; median weight: 7.4 kg, IQR: 5.8-13.3 kg) were included. They were grouped into shunt lesions (N = 26), obstructive lesions (N = 26), transposition of the great arteries (N = 5), and single ventricle (N = 12). N = 39 (57%) were primary repairs, and 56 (81%) had 1 CPB run. For RCA and LAD peak velocities, there was an increase from pre- to post-CPB in RCA peak 39 cm/s (IQR: 30-54 cm/s) to 65 cm/s (IQR: 47-81 cm/s), P < 0.001, mean CFR 1.52 (IQR: 1.25-1.81), and LAD peak 49 cm/s (IQR: 39-60 cm/s) to 70 cm/s (IQR: 52-90 cm/s), P < 0.001, mean CFR 1.48 (IQR: 1.14-1.77). Conclusions: Coronary flow velocities increase from pre- to post-CPB in congenital heart lesions. CFR is consistent across all lesions but is relatively low compared with the adult population.

Contexte: On ne dispose pas de données normatives sur les effets de la dérivation cardiopulmonaire (DCP) sur le débit coronarien mesuré au moyen d'une échocardiographie transœsophagienne Doppler chez des enfants présentant une cardiopathie congénitale. L'objectif de l'étude était d'examiner de manière prospective les effets de la DCP sur le débit coronarien avant et après l'intervention chez des enfants présentant une cardiopathie congénitale. Méthodologie: Tous les enfants ayant subi une intervention chirurgicale pour une cardiopathie congénitale à l'Hospital for Sick Children de Toronto étaient admissibles à l'étude, à l'exception de ceux ayant subi une intervention de Norwood ou une transplantation cardiaque, de même que les enfants pesant moins de 2,5 kg. Les résultats du test Doppler et la réserve coronarienne pour l'artère coronaire droite (ACD) et la branche antérieure de l'artère coronaire gauche (ACG) ont été obtenus. Des analyses multivariées ont été réalisées au moyen de modèles de régression linéaire, avec correction en fonction de l'âge et du temps de clampage total. Résultats: Entre mai 2017 et juin 2018, 69 enfants (âge médian au moment de la chirurgie : 0,7 an, intervalle interquartile (IIQ) : 0,4-3,7 ans; poids médian : 7,4 kg, IIQ : 5,8-13,3 kg) ont été inclus dans l'étude. Les sujets ont été répartis en quatre groupes : shunts (n = 26), lésions obstructives (n = 26), permutation des gros vaisseaux (n = 5) et ventricule unique (n = 12). Chez 39 sujets (57 %), il s'agissait d'une réparation primitive, et 56 enfants (81 %) avaient déjà subi une DCP. Les vitesses maximales dans l'ACD et dans la branche antérieure de l'ACG ont augmenté après la DCP, passant de 39 cm/s (IIQ : 30-54 cm/s) à 65 cm/s (IIQ : 47-81 cm/s), p < 0,001; réserve coronarienne moyenne : 1,52 (IIQ : 1,25-1,81) pour l'ACD, et de 49 cm/s (IIQ : 39-60 cm/s) à 70 cm/s (IIQ : 52-90 cm/s), p < 0,001; réserve coronarienne moyenne : 1,48 (IIQ : 1,14-1,77) pour la branche antérieure de l'ACG. Conclusions: Le débit coronarien augmente après une DCP dans les cas de lésions cardiaques congénitales. La réserve coronarienne est constante dans tous les types de lésions, mais elle est relativement faible comparativement à celle de la population adulte.

A Practical Approach to Invasive Testing in Ischemia With No Obstructive Coronary Arteries (INOCA).

Up to 65% of women and approximately 30% of men have ischemia with no obstructive coronary artery disease (CAD; commonly known as INOCA) on invasive coronary angiography performed for stable angina. INOCA can be due to coronary microvascular dysfunction or coronary vasospasm. Despite the absence of obstructive CAD, those with INOCA have an increased risk of all-cause mortality and adverse outcomes, including recurrent angina and cardiovascular events. These patients often undergo repeat testing, including cardiac catheterization, resulting in lifetime healthcare costs that rival those for obstructive CAD. Patients with INOCA often remain undiagnosed and untreated. This review discusses the symptoms and prognosis of INOCA, offers a systematic approach to the diagnostic evaluation of these patients, and summarizes therapeutic management, including tailored therapy according to underlying pathophysiological mechanisms.

Jusqu'à 65 % des femmes et environ 30 % des hommes présentent une ischémie sans coronaropathie obstructive (INOCA [ischemia with no obstructive coronary artery disease]) révélée à la faveur d'une angiographie coronarienne invasive réalisée pour une angine stable. L'INOCA peut être attribuable à une dysfonction microvasculaire coronaire ou à un vasospasme coronaire. Malgré l'absence de coronaropathie obstructive, les patients atteints d'une INOCA présentent un risque accru de décès toutes causes confondues et d'événements indésirables, notamment l'angine récurrente et des événements cardiovasculaires. Ces patients sont souvent soumis à des examens répétés, dont le cathétérisme cardiaque, ce qui représente des dépenses de santé à vie qui rivalisent avec celles associées aux coronaropathies obstructives. Dans bien des cas, l'INOCA échappe au diagnostic et n'est pas traité. Dans le présent article de synthèse, nous nous penchons sur les symptômes et le pronostic de l'INOCA. Nous proposons une méthode systématique d'évaluation diagnostique de ces patients et résumons les modalités de sa prise en charge thérapeutique, notamment un traitement adapté aux mécanismes physiopathologiques sous-jacents.

The myocardium of fetuses with endocardial fibroelastosis contains fewer B and T lymphocytes than normal control myocardium.

The observation that endocardial fibroelastosis (EFE) can result from an immune response to maternal autoantibody deposition in the fetal myocardium raises the possibility that the fetal immune system may contribute to the pathogenesis of idiopathic EFE and dilated cardiomyopathy (DCM). This study sought to characterize myocardial immune cell presence in fetuses and neonates with idiopathic EFE + DCM, in those with EFE + structural heart disease, and in normal control subjects. Paraffin tissue sections from fetuses identified from the pathology database were stained for B cell, T cell, macrophage, and general hematopoietic cell surface markers. Of the 14 fetuses included in the study, 5 had EFE + DCM, 4 had EFE + structural heart disease, and 5 were normal control fetuses. The EFE + DCM group had fewer B cells than the control group (0.15 vs. 0.44 cells/mm(2); p = 0.005). The EFE + heart disease group had both fewer B cells (0.18 vs. 0.44 cells/mm(2); p = 0.08) and T cells (0.29 vs. 0.80 cells/mm(2); p = 0.04) than the control group. The CD4/CD8 ratio was similar in the EFE + DCM and EFE + heart disease groups (1.0 vs. 0.9; p = 0.17) but higher in the EFE + DCM group than in the control group (0.9 vs. 0.3; p = 0.03). The myocardium of fetuses with EFE contains fewer B and T lymphocytes than normal control fetuses.

Characterization of the Human Coronary Microvascular Response to Multiple Hyperaemic Agents.

BACKGROUND: It is unclear whether the coronary microvascular responses to multiple, mechanistically distinct hyperaemic agents exert similar dilatory responses or share common clinical predictors. This study therefore sought to characterize the index of microvascular resistance (IMR) response to multiple hyperaemic agents in the human coronary circulation. METHODS: Thermodilution-derived IMR was determined during intravenous adenosine, intracoronary acetylcholine, and intravenous dobutamine in patients with ischemic symptoms and nonobstructive coronary angiograms. A total of 128 patients were studied (44 with adenosine and acetylcholine, and 84 with all agents). Adenosine IMR >25, acetylcholine IMR >31, and dobutamine IMR >29 were used to define elevated responses. RESULTS: IMR responses demonstrated weak-to-moderate association (adenosine vs acetylcholine IMR: ρ = 0.33; adenosine vs dobutamine IMR: ρ = 0.51; acetylcholine vs dobutamine IMR: ρ = 0.28; all P < 0.01). Logistic regression analyses revealed that: (1) elevated adenosine IMR was associated with increasing age and left ventricle hypertrophy (odds ratio [OR] = 1.27 and 1.58; both P < 0.05, respectively), (2) elevated acetylcholine IMR was associated with increasing plasma uric acid (OR = 1.09; P < 0.05), and (3) elevated dobutamine IMR was associated with hypertension and left atrial volume index (OR = 3.99 and 1.07; both P < 0.05, respectively). Subset analyses to evaluate clinical utility of the acetylcholine and dobutamine IMR, independent of abnormal adenosine IMR, revealed that elevated acetylcholine and/or dobutamine IMR were associated with higher risk exercise stress tests, left atrial volumes, and burden of exertional chest pain. CONCLUSIONS: Microvascular-specific IMR responses to different hyperaemic agents are only moderately associated, whereas the predictors for agent-specific IMR responses varied, suggesting that multiple pharmacologic agents interrogate different microvascular control mechanisms.

CONTEXTE: On ne sait pas vraiment si les réponses microvasculaires coronariennes à de multiples agents hyperémiques aux modes d'action distincts ont des effets vasodilatateurs similaires ou partagent des facteurs prédictifs cliniques communs. Cette étude visait donc à caractériser la réponse selon l'indice de résistance microvasculaire (IMR) aux multiples agents hyperémiques dans la circulation coronarienne chez l'humain. MÉHODOLOGIE: L'IMR obtenu par thermodilution a été déterminé pendant l'administration intraveineuse d'adénosine, intracoronarienne d'acétylcholine et intraveineuse de dobutamine chez des patients présentant des symptômes ischémiques et par angiogrammes coronariens non obstructifs. Un total de 128 patients (44 avec l'adénosine et l'acétylcholine, et 84 avec tous les agents) ont fait partie de l'étude. Des réponses élevées étaient définies par un IMR à l'adénosine > 25, un IMR à l'acétylcholine > 31 et un IMR à la dobutamine > 29. RÉSULTATS: Les réponses selon l'IMR ont révélé une association faible à modérée (IMR à l'adénosine vs IMR à l'acétylcholine : ρ = 0,33; IMR à l'adénosine vs IMR à la dobutamine : ρ = 0,51; IMR à l'acétylcholine vs IMR à la dobutamine : ρ = 0,28; tous : p < 0,01). Des analyses de régression logistique ont révélé que : 1) un IMR à l'adénosine élevé était associé à l'avancement en âge et à une hypertrophie ventriculaire gauche (rapport des cotes [RC] = 1,27 et 1,58; p < 0,05 respectivement pour les deux), 2) un IMR à l'acétylcholine élevé était associé à l'augmentation de la concentration plasmatique d'acide urique (RC = 1,09; p < 0,05) et 3) un IMR à la dobutamine élevé était associé à l'hypertension et à l'indice de volume auriculaire gauche (RC = 3,99 et 1,07; p < 0,05 respectivement pour les deux). Des analyses par sous-groupes visant à évaluer l'utilité clinique de l'IMR à l'acétylcholine et à la dobutamine, indépendamment d'un IMR à l'adénosine anormal, ont révélé que des IMR à l'acétylcholine et/ou à la dobutamine élevés étaient associés à une augmentation du risque lors des épreuves à l'effort, à un volume auriculaire gauche plus élevé et à une augmentation du fardeau associé à la douleur thoracique à l'effort. CONCLUSIONS: Les réponses microvasculaires selon l'IMR à différents agents hyperémiques sont seulement modérément associées, alors que les facteurs prédictifs des réponses selon l'IMR spécifique de l'agent varient, ce qui laisse croire que les multiples agents pharmacologiques font appel à différents mécanismes de contrôle microvasculaire.

Acetylcholine acutely modifies nitric oxide synthase function in the human coronary circulation.

Intracoronary infusions of acetylcholine (ACh) and the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-l-arginine (l-NMMA) are routinely used to assess endothelial function in the human coronary circulation. Currently, there are no studies that examine whether the response to one of these agents predicts the response to the other in a given individual. We sought to determine whether human coronary vasomotor responses to intracoronary ACh are predictive of the response to intracoronary l-NMMA. Following diagnostic coronary angiography, a coronary sinus catheter was placed. Sequential intracoronary infusions of ACh and l-NMMA were performed in 14 patients without severe coronary artery disease (CAD). In nine patients with severe CAD, only l-NMMA was infused. Quantitative coronary angiography was performed immediately following infusions to determine changes in coronary diameter. Coronary sinus oxygen saturation and the transcardiac oxygen saturation gradients were determined during infusions as an index of coronary blood flow (CBF). There were no significant differences in the prevalence of hypertension, diabetes, smoking or plasma creatinine or cholesterol levels between patients with and without severe CAD. In the 14 patients without severe CAD, ACh reduced coronary diameter on average by 8% (from 2.7 ± 0.8 to 2.5 ± 0.8 mm, P = 0.003) and reduced the transcardiac oxygen saturation gradient from 63 ± 8 to 42 ± 16% (P = 0.0001). N(G)-Monomethyl-l-arginine had no significant effect on coronary diameter (from 2.7 ± 0.8 to 2.7 ± 0.8 mm, n.s.) and did not alter the transcardiac oxygen saturation gradient (from 63 ± 8 to 63 ± 7%, n.s.). A positive rather than negative correlation was observed between the ACh- and l-NMMA-induced changes in coronary diameter (r = 0.752, P = 0.0002). In nine patients with severe CAD who did not receive ACh, l-NMMA had no effect on coronary diameter but produced an increased transcardiac oxygen saturation gradient consistent with reduced CBF (from 58 ± 5 to 62 ± 4%, P = 0.003). The CBF response to l-NMMA was significantly different between the two groups (P = 0.002). The failure of l-NMMA to reduce CBF following ACh infusion, in contrast to the results seen in the l-NMMA-only group, suggests that NOS had been rendered dysfunctional by the ACh infusion itself. The positive correlation in changes to coronary diameter between ACh and l-NMMA suggests that the degree of NOS dysfunction was directly correlated to the degree of preceding activation by ACh. Combined, these unexpected results suggest that ACh administration may acutely modify the function of NOS in the human coronary circulation.

Early Observations During the COVID-19 Pandemic in Cardiac Catheterization Procedures for ST-Elevation Myocardial Infarction Across Ontario.

BACKGROUND: In response to the COVID-19 pandemic, Ontario issued a declaration of emergency, implementing public health interventions on March 16, 2020. METHODS: We compared cardiac catheterization procedures for ST-elevation myocardial infarction (STEMI) between January 1 and May 10, 2020 to the same time frame in 2019. RESULTS: From March 16 to May 10, 2020, after implementation of provincial directives, STEMI cases significantly decreased by up to 25%. The proportion of patients who achieved guideline targets for first medical contact balloon for primary percutaneous coronary intervention (PCI) decreased substantially to 28% (median, 101 minutes) for patients who presented directly to a PCI site and to 37% (median, 149 minutes) for patients transferred from a non-PCI site, compared with 2019. CONCLUSIONS: STEMI cases across Ontario have been substantially affected during the COVID-19 pandemic.

INTRODUCTION: En réponse à la pandémie de COVID-19, l'Ontario a déclaré l'état d'urgence et mis en place des interventions de santé publique le 16 mars 2020. MÉTHODES: Nous avons comparé les procédures de cathétérisme cardiaque lors d'infarctus du myocarde avec sus-décalage du segment ST (STEMI) du 1er janvier au 10 mai 2020 à la même période en 2019. RÉSULTATS: Du 16 mars au 10 mai 2020, après la mise en place des directives provinciales, les cas de STEMI ont connu une diminution significative pouvant atteindre jusqu'à 25 %. La proportion de patients qui ont atteint les objectifs prévus aux lignes directrices entre le premier contact médical et le ballonnet de l'intervention coronarienne percutanée (IPC) a connu une diminution considérable de 28 % (médiane, 101 minutes) pour ceux qui se présentaient directement dans un site d'IPC et de 37 % (médiane, 149 minutes) pour ceux qui étaient dirigés vers un site non-ICP, et ce, en comparaison à 2019. CONCLUSIONS: La pandémie de COVID-19 a considérablement nui aux cas de STEMI de l'Ontario.

Improving Prenatal Diagnosis of Coarctation of the Aorta.

BACKGROUND: The purpose of the study was to evaluate the association between fetal echocardiographic measurements and the need for intervention (primary coarctation repair, staged coarctation repair, or catheter intervention) in prenatally diagnosed coarctation of the aorta. METHODS: A single-centre retrospective cohort study (2005-2015) of 107 fetuses diagnosed with suspected coarctation of the aorta in the setting of an apex-forming left ventricle and antegrade flow across the mitral and aortic valves. RESULTS: Median gestational age at diagnosis was 32 weeks (interquartile range, 23-35 weeks). Fifty-six (52%) did not require any neonatal intervention, 51 patients (48%) underwent a biventricular repair. In univariable analysis, an increase in ascending aorta (AAo) peak Doppler flow velocity (odds ratio [OR], 1.40 [95% confidence interval [CI], 1.05-1.91] per 20 cm/s; P = 0.03) was associated with intervention. No intervention was associated with larger isthmus size (OR, 0.23; P < 0.001), transverse arch diameter (OR, 0.23; P < 0.001), and aortic (OR, 0.72; P = 0.02), mitral (OR, 0.58; P = 0.001), and AAo (OR, 0.53; P < 0.001) z-scores. In multivariable analysis, higher peak AAo Doppler (OR, 2.51 [95% CI, 1.54-4.58] per 20 cm/s; P = 0.001) and younger gestational age at diagnosis (OR, 0.81 [95% CI, 0.70-0.93] per week; P = 0.005) were associated with intervention, whereas a higher AAo z-score (OR, 0.65 [95% CI, 0.43-0.94] per z; P = 0.029) and transverse arch dimension (OR, 0.44 [95% CI, 0.18-0.97]; P = 0.05) decreased the risk of intervention. CONCLUSIONS: In prenatally suspected coarctation, the variables associated with intervention comprised smaller AAo and transverse arch size, earlier gestational age at diagnosis, and the additional finding of a higher peak AAo Doppler.

Coronary artery Doppler patterns are associated with clinical outcomes post-arterial switch operation for transposition of the great arteries.

Aims: Transposition of the great arteries (TGA) is generally repaired using the arterial switch operation (ASO) involving coronary transfer. The objective of this prospective study was to determine whether specific coronary Doppler patterns intra-operatively predicted adverse early myocardial events. Methods and results: Patients < 3 months old with TGA undergoing the ASO were eligible. All patients (when feasible) underwent an intra-operative transoesophageal echo (TEE) plus an epicardial echo and had pre-op, early post-op, pre-discharge and follow-up functional echocardiograms. The primary endpoint was a composite myocardial ischaemic event (any of: post-operative ST changes, ventricular tachycardia, need for extracorporeal membrane oxygenation (ECMO). Associations of coronary Doppler flow patterns with outcomes were modelled with logistic regression models. From May 2009 to December 2012, 40 patients (29 male, birth weight 3.29 ± 0.58 kg) were recruited. n = 32 had TEE + epicardial, four TEE only, four epicardial only. Seven (18%) patients had an adverse myocardial event (five ST changes, two ventricular tachycardia (one also ECMO). There was one death. n = 3 had a coronary artery (CA) revision post-operatively, and three had re-operation for non-CA causes. By TEE, flow reversal in the left coronary artery was associated with the composite endpoint [Odds Ratio (OR) 31.5, P = 0.004], and for chest open > 3 days (OR 6.67, P = 0.0537). Coronary Doppler flow patterns were similar by TEE and epicardial echo. The tissue Doppler parameters showed an early post-op decrease (P < 0.001 for all measures), with full recovery at follow-up in 31/37 cases. Conclusion: Intra-operative evaluation of coronary artery flow patterns should be considered for patients undergoing the ASO.

Borderline left ventricles in prenatally diagnosed atrioventricular septal defect or double outlet right ventricle: echocardiographic predictors of biventricular repair.

BACKGROUND: Atrioventricular septal defect (AVSD) and double outlet right ventricle (DORV) with normally related great arteries and normal ventricular sizes are associated with a good long-term prognosis after biventricular (BV) repair. The outcome of cases with a borderline small left ventricle (bLV) is unclear. The purpose of the study was to retrospectively determine echocardiographic predictors of successful BV repair in fetuses with AVSD or DORV with a bLV. METHODS AND RESULTS: From 1991 to 2004, 24 fetuses with AVSD plus bLV and 24 with DORV plus bLV were identified. Fetal echocardiographic parameters comparing BV repair versus single ventricle (SV) palliation were obtained, including the presence or absence of an apex-forming bLV was recorded. A bLV was defined as a right ventricular/left ventricular end-diastolic dimension ratio between 2 and 4 SDs for gestational age. The overall survival from fetal diagnosis was 21% (5/24) for AVSD/bLV and 13% (3/24) for DORV/bLV. Of 11 liveborns with AVSD/bLV and 8 liveborns with DORV/bLV, 6 underwent BV repair (5 survivors), 7 SV palliation (3 survivors), and 1 cardiac transplant. Five infants receiving compassionate care only were excluded from the analysis. Parameters such as ratio of valve annuli, ventricular end-diastolic dimensions, degree of valve regurgitation, and the presence of endocardial fibroelastosis were not too predictive of outcome. The presence of an apex-forming bLV was the only predictor of BV repair (6/6 BV repair vs 2/8 SV palliation, P < .05). CONCLUSIONS: Prenatally diagnosed AVSD or DORV with bLV has a very poor prognosis. An apex-forming bLV predicts successful BV repair and is an important prognostic indicator.