Management of Adults With Anomalous Aortic Origin of the Coronary Arteries: State-of-the-Art Review.

As a result of increasing adoption of imaging screening, the number of adult patients with a diagnosis of anomalous aortic origin of the coronary arteries (AAOCA) has grown in recent years. Existing guidelines provide a framework for management and treatment, but patients with AAOCA present with a wide range of anomalies and symptoms that make general recommendations of limited applicability. In particular, a large spectrum of interventions can be used for treatment, and there is no consensus on the optimal approach to be used. In this paper, a multidisciplinary group of clinical and interventional cardiologists and cardiac surgeons performed a systematic review and critical evaluation of the available evidence on the interventional treatment of AAOCA in adult patients. Using a structured Delphi process, the group agreed on expert recommendations that are intended to complement existing clinical practice guidelines.

Management of Adults With Anomalous Aortic Origin of the Coronary Arteries: State-of-the-Art Review.

As a result of increasing adoption of imaging screening, the number of adult patients with a diagnosis of anomalous aortic origin of the coronary arteries (AAOCA) has grown in recent years. Existing guidelines provide a framework for management and treatment, but patients with AAOCA present with a wide range of anomalies and symptoms that make general recommendations of limited applicability. In particular, a large spectrum of interventions can be used for treatment, and there is no consensus on the optimal approach to be used. In this paper, a multidisciplinary group of clinical and interventional cardiologists and cardiac surgeons performed a systematic review and critical evaluation of the available evidence on the interventional treatment of AAOCA in adult patients. Using a structured Delphi process, the group agreed on expert recommendations that are intended to complement existing clinical practice guidelines.

Myocardial Contractile Mechanics in Ischemic Mitral Regurgitation: Multicenter Data Using Stress Perfusion Cardiovascular Magnetic Resonance.

BACKGROUND: Left ventricular (LV) ischemia has been variably associated with functional mitral regurgitation (FMR). Determinants of FMR in patients with ischemia are poorly understood. OBJECTIVES: This study sought to test whether contractile mechanics in ischemic myocardium underlying the mitral valve have an impact on likelihood of FMR. METHODS: Vasodilator stress perfusion cardiac magnetic resonance was performed in patients with coronary artery disease (CAD) at multiple centers. FMR severity was confirmed quantitatively via core lab analysis. To test relationship of contractile mechanics with ischemic FMR, regional wall motion and strain were assessed in patients with inducible ischemia and minimal (≤5% LV myocardium, nontransmural) infarction. RESULTS: A total of 2,647 patients with CAD were studied; 34% had FMR (7% moderate or greater). FMR severity increased with presence (P < 0.001) and extent (P = 0.01) of subpapillary ischemia: patients with moderate or greater FMR had more subpapillary ischemia (odds ratio [OR]: 1.13 per 10% LV; 95% CI: 1.05-1.21; P = 0.001) independent of ischemia in remote regions (P = NS); moderate or greater FMR prevalence increased stepwise with extent of ischemia and infarction in subpapillary myocardium (P < 0.001); stronger associations between FMR and infarction paralleled greater wall motion scores in infarct-affected territories. Among patients with inducible ischemia and minimal infarction (n = 532), wall motion and radial strain analysis showed impaired subpapillary contractile mechanics to associate with moderate or greater FMR (P < 0.05) independent of remote regions (P = NS). Conversely, subpapillary ischemia without contractile dysfunction did not augment FMR likelihood. Mitral and interpapillary dimensions increased with subpapillary radial strain impairment; each remodeling parameter associated with impaired subpapillary strain (P < 0.05) independent of remote strain (P = NS). Subpapillary radial strain (OR: 1.13 per 5% [95% CI: 1.02-1.25]; P = 0.02) and mitral tenting area (OR: 1.05 per 10 mm2 [95% CI: 1.00-1.10]; P = 0.04) were associated with moderate or greater FMR controlling for global remodeling represented by LV end-systolic volume (P = NS): when substituting sphericity for LV volume, moderate or greater FMR remained independently associated with subpapillary radial strain impairment (OR: 1.22 per 5% [95% CI: 1.02-1.47]; P = 0.03). CONCLUSIONS: Among patients with CAD and ischemia, FMR severity and adverse mitral apparatus remodeling increase in proportion to contractile dysfunction underlying the mitral valve.

Ischemia-Mediated Dysfunction in Subpapillary Myocardium as a Marker of Functional Mitral Regurgitation.

OBJECTIVES: The goal of this study was to test whether ischemia-mediated contractile dysfunction underlying the mitral valve affects functional mitral regurgitation (FMR) and the prognostic impact of FMR. BACKGROUND: FMR results from left ventricular (LV) remodeling, which can stem from myocardial tissue alterations. Stress cardiac magnetic resonance can assess ischemia and infarction in the left ventricle and papillary muscles; relative impact on FMR is uncertain. METHODS: Vasodilator stress cardiac magnetic resonance was performed in patients with known or suspected coronary artery disease at 7 sites. Images were centrally analyzed for MR etiology/severity, mitral apparatus remodeling, and papillary ischemia. RESULTS: A total of 8,631 patients (mean age 60.0 ± 14.1 years; 55% male) were studied. FMR was present in 27%, among whom 16% (n = 372) had advanced (moderate or severe) FMR. Patients with ischemia localized to subpapillary regions were more likely to have advanced FMR (p = 0.003); those with ischemia localized to other areas were not (p = 0.17). Ischemic/dysfunctional subpapillary myocardium (odds ratio: 1.24/10% subpapillary myocardium; confidence interval: 1.17 to 1.31; p < 0.001) was associated with advanced FMR controlling for infarction. Among a subgroup with (n = 372) and without (n = 744) advanced FMR matched (1:2) on infarct size/distribution, patients with advanced FMR had increased adverse mitral apparatus remodeling, paralleled by greater ischemic/dysfunctional subpapillary myocardium (p < 0.001). Although posteromedial papillary ischemia was more common with advanced FMR (p = 0.006), subpapillary ischemia with dysfunction remained associated (p < 0.001), adjusting for posteromedial papillary ischemia (p = 0.074). During follow-up (median 5.1 years), 1,473 deaths occurred in the overall cohort; advanced FMR conferred increased mortality risk (hazard ratio: 1.52; 95% confidence interval: 1.25 to 1.86; p < 0.001) controlling for left ventricular ejection fraction, infarction, and ischemia. CONCLUSIONS: Ischemic and dysfunctional subpapillary myocardium provides a substrate for FMR, which predicts mortality independent of key mechanistic substrates.

Effect of Ventricular Pacing on Morbidity in Adults After Fontan Repair.

Implantation of a permanent pacemaker is a negative prognostic marker in patients with Fontan palliation; however, data delineating outcomes in adult patients with pacemaker requirements are lacking. We hypothesize that high ventricular pacing burden is associated with adverse outcomes in adult Fontan patients. We performed a retrospective review comprising adult patients with history of Fontan repair. A high burden of ventricular pacing was defined as ≥40% pacing. Major adverse clinical events (MACE) were defined as all-cause mortality or need for advanced cardiac therapies (ventricular assist device or heart transplant). A total of 145 adult patients with Fontan were studied for a median of 3.1 years. Twenty (14%) patients had implanted pacemakers with ≥40% ventricular pacing. Twelve events occurred in those with ≥40% ventricular pacing (incidence 60.0%) versus 11 in those without (incidence 8.8%). In multivariable analysis, ≥40% ventricular-pacing (odds ratio 12.51, confidence interval [CI] 3.56 to 43.83, p <0.001) was associated with MACE independent of initial Fontan type, New York Heart Association functional class at baseline, or history of atrial tachyarrythmia. In survival analysis, patients with ≥40% ventricular pacing had nearly 8 times the risk of MACE compared with those with a lower ventricular pacing burden (hazard ratio 7.79, 95% CI 2.56 to 23.66, p <0.001), whereas patients with atrial-only or <40% ventricular pacing burden had a trend toward higher hazard of MACE compared with those without permanent pacemaker (hazard ratio 3.38, 95% CI 0.92 to 12.47, p = 0.07) that did not meet statistical significance. These findings suggest that high ventricular pacing burden contributes to poor outcomes in the adult Fontan patients and bear consideration when determining optimal treatment of tachyarrhythmias in this population.

Clinical and echocardiographic features of paradoxical low-flow and normal-flow severe aortic stenosis patients with concomitant mitral regurgitation.

Mitral regurgitation (MR) coexists in a significant proportion of patients with severe aortic stenosis (AS), and portends inferior therapeutic outcomes. In severe AS, MR is thought to contribute to a low-flow state by decreasing forward stroke volume. We investigated concomitant MR on the clinical and echocardiographic features of patients with "paradoxical" low-flow (PLF) and normal-flow (NF) severe AS. Clinical and echocardiographic profiles of 886 consecutive patients with index echocardiographic diagnosis of severe AS (AVA < 1.0 cm2) were analysed retrospectively. All patients had preserved ejection fraction (LVEF ≥ 50%, n = 645), and were divided into PLF (stroke volume index, SVI < 35 mL/m2) and NF AS. They were then further subdivided based on the presence or absence of moderate-or-severe MR (msMR). A higher prevalence of concomitant msMR was observed in patients with PLF AS (14.9%; n = 33/221) compared to those with NF AS (8.0%; n = 34/424). Concomitant msMR was associated with echocardiographic features of increased diastolic dysfunction in both PLF AS and NF AS patients, as evidenced by increased LA diameter (PLF AS 52.9 ± 12.5 to 43.9 ± 8.9 mm; NF AS 29.6 ± 10.8 to 42.4 ± 8.8 mm; p < 0.001) and increased transmitral E/A ratio (PLF AS 1.26 ± 0.56 to 0.92 ± 0.43; NF AS 1.19 ± 0.63 to 0.94 ± 0.45; p = 0.004). Amongst patients with NF AS, msMR was additionally associated with increased E:e' ratio (25.5 ± 15.1 vs 19.3 ± 10.8; p = 0.025). Concomitant MR was more common in PLF AS compared to NF. Although possibly related to the MR, patients severe AS and MR appeared to have more severe diastolic dysfunction. Further studies are warranted to evaluate prognosis and guide management.

Q wave area for stratification of global left ventricular infarct size: comparison to conventional ECG assessment using Selvester QRS-score.

OBJECTIVES: Left ventricular (LV) infarct size is a prognostic determinant after acute myocardial infarction (AMI). ECG data have been used to measure infarct size, but conventional approaches use multiparametric algorithms that have limited clinical applicability. This study tested a novel ECG approach - based solely on Q wave area - for calculation of LV infarct size. METHODS: Serial 12-lead ECGs were performed in AMI patients. Computerized software was used to quantify Q wave area (summed across surface ECG leads) and Selvester QRS-score components. ECG analysis was compared to the reference of myocardial infarct size quantified by delayed enhancement cardiac magnetic resonance. RESULTS: Overall, 158 patients underwent ECG during early (4±0.4) and follow-up (29±5 days) post-AMI time points. Selvester QRS-score and Q wave area increased stepwise with LV infarct size (P<0.001). Whereas both methods manifested marked increases at a threshold of 10% LV infarction, magnitude was greater for Q wave area (>2.5-fold) than Selvester QRS-score (

P wave area for quantitative electrocardiographic assessment of left atrial remodeling.

BACKGROUND: Left atrial (LA) dilation provides a substrate for mitral regurgitation (MR) and atrial arrhythmias. ECG can screen for LA dilation but standard approaches do not assess LA geometry as a continuum, as does non-invasive imaging. This study tested ECG-quantified P wave area as an index of LA geometry. METHODS AND RESULTS: 342 patients with CAD underwent ECG and CMR within 7 (0.1±1.4) days. LA area on CMR correlated best with P wave area in ECG lead V1 (r = 0.42, p<0.001), with lesser correlations for P wave amplitude and duration. P wave area increased stepwise in relation to CMR-evidenced MR severity (p<0.001), with similar results for MR on echocardiography (performed in 86% of patients). Pulmonary arterial (PA) pressure on echo was increased by 50% among patients in the highest (45±14 mmHg) vs. the lowest (31±9 mmHg) P wave area quartile of the population. In multivariate regression, CMR and echo-specific models demonstrated P wave area to be independently associated with LA size after controlling for MR, as well as echo-evidenced PA pressure. Clinical follow-up (mean 2.4±1.9 years) demonstrated ECG and CMR to yield similar results for stratification of arrhythmic risk, with a 2.6-fold increase in risk for atrial fibrillation/flutter among patients in the top P wave area quartile of the population (CI 1.1-5.9, p = 0.02), and a 3.2-fold increase among patients in the top LA area quartile (CI 1.4-7.0, p = 0.005). CONCLUSIONS: ECG-quantified P wave area provides an index of LA remodeling that parallels CMR-evidenced LA chamber geometry, and provides similar predictive value for stratification of atrial arrhythmic risk.

Left ventricular geometric remodeling in relation to non-ischemic scar pattern on cardiac magnetic resonance imaging.

Left ventricular (LV) remodeling and myocardial fibrosis have been linked to adverse heart failure outcomes. Mid wall late gadolinium enhancement (MW-LGE) on cardiac magnetic resonance (CMR) imaging is well-associated with non-ischemic cardiomyopathy (NICM), but prevalence in ischemic cardiomyopathy (ICM) and association with remodeling are unknown. The population comprised patients with systolic dysfunction [LV ejection fraction (LVEF ≤ 40 %)]. CMR was used to identify MW-LGE, conventionally defined as fibrosis of the mid-myocardial or epicardial aspect of the LV septum. 285 patients were studied. MW-LGE was present in 12 %, and was tenfold more common with NICM (32 %) versus ICM (3 %, p < 0.001). However, owing to higher prevalence of ICM, 15 % of patients with MW-LGE had ICM. LV wall stress was higher (p = 0.02) among patients with, versus those without, MW-LGE despite similar systolic blood pressure (p = 0.24). In multivariate analysis, MW-LGE was associated with CMR-quantified LV end-diastolic volume (p = 0.03) independent of LVEF and mass. Incorporation of clinical and imaging variables demonstrated MW-LGE to be associated with higher LV end-diastolic volume (OR 1.13, CI 1.004-1.27 per 10 ml/m(2), p = 0.04) after controlling for presence of NICM (OR 16.0, CI 5.8-44.1, p < 0.001). While more common in NICM, MW-LGE can occur in ICM and is a marker of LV chamber dilation irrespective of cardiomyopathic etiology.

Usefulness of Q-wave area for threshold-based stratification of global left ventricular myocardial infarct size.

Left ventricular (LV) infarct size affects prognosis after acute myocardial infarction (AMI). Delayed enhancement cardiac magnetic resonance (DE-CMR) provides accurate infarct quantification but is unavailable or contraindicated in many patients. This study tested whether simple electrocardiography (ECG) parameters can stratify LV infarct size. One hundred fifty-two patients with AMI underwent DE-CMR and serial 12-lead ECG. Electrocardiograms were quantitatively analyzed for multiple aspects of Q-wave morphology, including duration, amplitude, and geometric area (QWAr) summed across all leads except aVR. Patients with pathologic Q waves had larger infarcts measured by DE-CMR or enzymes (both p <0.001), even after controlling for infarct distribution by CMR or x-ray angiography. Comparison between early (4 ± 0.4 days after AMI) and follow-up (29 ± 6 days) ECG demonstrated temporal reductions in Q-wave amplitude (1.8 ± 1.4 vs 1.6 ± 1.6 mV; p = 0.03) but not QWAr (41 ± 38 vs 39 ± 43 mV•ms; p = 0.29). At both times, QWAr augmented stepwise with DE-CMR quantified infarct size (p <0.001). QWAr increased markedly at 10% LV infarct threshold, with differences more than threefold on early ECG (59 ± 39 vs 18 ± 20 mV•ms; p <0.001) and nearly fivefold (59 ± 46 vs 13 ± 16 mV•ms; p <0.001) on follow-up. Diagnostic performance compared with a 10% infarction cutoff was good on early (area under the curve = 0.84) and follow-up (area under the curve = 0.87) ECG. Optimization of sensitivity (95% to 98%) enabled QWAr to exclude affected patients with 90% to 94% negative predictive value at each time point. In conclusion, LV infarct size is accompanied by stepwise increments in Q-wave morphology, with QWAr increased three- to fivefold at a threshold of 10% LV infarction. Stratification based on QWAr provides excellent negative predictive value for exclusion of large (≥10%) LV infarct burden.