Aortic valve replacement versus conservative treatment in asymptomatic severe aortic stenosis: long-term follow-up of the AVATAR trial.

BACKGROUND AND AIMS: The question of when and how to treat truly asymptomatic patients with severe aortic stenosis (AS) and normal left ventricular (LV) systolic function is still subject to debate and ongoing research. Here, the results of extended follow-up of the AVATAR trial are reported (NCT02436655, clinical trials.gov). METHODS: The AVATAR trial randomly assigned patients with severe, asymptomatic AS and LV ejection fraction ≥50% to undergo either early surgical aortic valve replacement (AVR) or conservative treatment with watchful waiting strategy. All patients had negative exercise stress testing. The primary hypothesis was that early AVR will reduce a primary composite endpoint comprising all-cause death, acute myocardial infarction, stroke or unplanned hospitalization for heart failure (HF), as compared to conservative treatment strategy. RESULTS: A total of 157 low-risk patients (mean age 67 years, 57% men, mean Society of Thoracic Surgeons score 1.7%) were randomly allocated to either early AVR group (n=78) or conservative treatment group (n=79). In an intention-to-treat analysis, after a median follow-up of 63 months, the primary composite endpoint outcome event occurred in 18/78 patients (23.1%) in the early surgery group and in 37/79 patients (46.8%) in the conservative treatment group (hazard ratio [HR] early surgery vs. conservative treatment 0.42; 95% confidence interval [CI] 0.24-0.73, p=0.002). The Kaplan-Meier estimates for individual endpoints of all-cause death and HF hospitalization were significantly lower in the early surgery compared with the conservative group (HR 0.44; 95% CI 0.23-0.85, p=0.012 for all-cause death, and HR 0.21; 95% CI 0.06-0.73, p=0.007 for HF hospitalizations). CONCLUSIONS: The extended follow-up of the AVATAR trial demonstrates better clinical outcomes with early surgical AVR in truly asymptomatic patients with severe AS and normal LV ejection fraction compared with patients treated with conservative management on watchful waiting. TRIAL REGISTRATION NUMBER: NCT02436655 (ClinicalTrials.gov).

Artificial Intelligence-Enabled Quantitative Coronary Plaque and Hemodynamic Analysis for Predicting Acute Coronary Syndrome.

BACKGROUND: A lesion-level risk prediction for acute coronary syndrome (ACS) needs better characterization. OBJECTIVES: This study sought to investigate the additive value of artificial intelligence-enabled quantitative coronary plaque and hemodynamic analysis (AI-QCPHA). METHODS: Among ACS patients who underwent coronary computed tomography angiography (CTA) from 1 month to 3 years before the ACS event, culprit and nonculprit lesions on coronary CTA were adjudicated based on invasive coronary angiography. The primary endpoint was the predictability of the risk models for ACS culprit lesions. The reference model included the Coronary Artery Disease Reporting and Data System, a standardized classification for stenosis severity, and high-risk plaque, defined as lesions with ≥2 adverse plaque characteristics. The new prediction model was the reference model plus AI-QCPHA features, selected by hierarchical clustering and information gain in the derivation cohort. The model performance was assessed in the validation cohort. RESULTS: Among 351 patients (age: 65.9 ± 11.7 years) with 2,088 nonculprit and 363 culprit lesions, the median interval from coronary CTA to ACS event was 375 days (Q1-Q3: 95-645 days), and 223 patients (63.5%) presented with myocardial infarction. In the derivation cohort (n = 243), the best AI-QCPHA features were fractional flow reserve across the lesion, plaque burden, total plaque volume, low-attenuation plaque volume, and averaged percent total myocardial blood flow. The addition of AI-QCPHA features showed higher predictability than the reference model in the validation cohort (n = 108) (AUC: 0.84 vs 0.78; P < 0.001). The additive value of AI-QCPHA features was consistent across different timepoints from coronary CTA. CONCLUSIONS: AI-enabled plaque and hemodynamic quantification enhanced the predictability for ACS culprit lesions over the conventional coronary CTA analysis. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary Computed Tomography Angiography and Computational Fluid Dynamics II [EMERALD-II]; NCT03591328).

Rationale and design of the ELEANOR trial early aortic valve surgery versus watchful waiting strategy in severe asymptomatic aortic regurgitation, ACRONYM: ELEANOR.

Background: The optimal treatment of patients with severe symptomatic aortic regurgitation (AR) is state-of-the-art surgery. Asymptomatic patients with advanced left ventricular (LV) dilatation and/or impaired ejection fraction should undergo surgical treatment, but there is no guidelines consensus on cut-off values for this recommendation. Multimodality imaging has brought new tools for the accurate selection of asymptomatic patients at risk of early clinical deterioration, however, prospective and randomized data are pending. Cardiac magnetic resonance (CMR)-derived AR quantification along with LV remodeling assessment appears to be the most accurate tool for a selection of such patients at risk. Trial design: The objective of our prospective and multicenter study is to determine whether patients at risk of early clinical deterioration as per CMR assessment will benefit from early surgical treatment. The study is designed as a superiority trial to demonstrate that early surgical treatment is safe and more effective than the standard treatment. A total of 217 asymptomatic patients with severe AR, but without current guidelines-based surgical indication, will be enrolled across all centers. We expect 24 % of patients identified as high clinical risk and therefore eligible for 1:1 randomization to early surgical treatment within 3 months or a watchful waiting strategy. Follow-up will be annual. We expect a complete restoration of LV size and function along with improved quality of life and physical performance in a short-term follow-up of 12 months. The primary endpoint will be a composite safety and efficacy with all criteria mandatory: 15 % or larger reduction of baseline CMR-derived LV end-diastolic volume index, LV ejection fraction >50 %, and no major adverse cardiovascular events. The annual follow-up will continue for a minimum of 4 years until the required number of endpoints is achieved to show a statistically significant difference in cardiovascular morbidity and mortality in early surgically treated patients. Conclusion: The ELEANOR trial is the first multicenter randomized controlled study to compare early surgical treatment with a watchful waiting strategy in asymptomatic patients with chronic severe AR at high risk of early clinical deterioration as per CMR assessment but without guidelines-based indications for surgical treatment.

Fibrosis and expression of extracellular matrix proteins in human interventricular septum in aortic valve stenosis and regurgitation.

Valvular heart disease leads to ventricular pressure and/or volume overload. Pressure overload leads to fibrosis, which might regress with its resolution, but the limits and details of this reverse remodeling are not known. To gain more insight into the extent and nature of cardiac fibrosis in valve disease, we analyzed needle biopsies taken from the interventricular septum of patients undergoing surgery for valve replacement focusing on the expression and distribution of major extracellular matrix protein involved in this process. Proteomic analysis performed using mass spectrometry revealed an excellent correlation between the expression of collagen type I and III, but there was little correlation with the immunohistochemical staining performed on sister sections, which included antibodies against collagen I, III, fibronectin, sarcomeric actin, and histochemistry for wheat germ agglutinin. Surprisingly, the immunofluorescence intensity did not correlate significantly with the gold standard for fibrosis quantification, which was performed using Picrosirius Red (PSR) staining, unless multiplexed on the same tissue section. There was also little correlation between the immunohistochemical markers and pressure gradient severity. It appears that at least in humans, the immunohistochemical pattern of fibrosis is not clearly correlated with standard Picrosirius Red staining on sister sections or quantitative proteomic data, possibly due to tissue heterogeneity at microscale, comorbidities, or other patient-specific factors. For precise correlation of different types of staining, multiplexing on the same section is the best approach.

Predictors of percutaneous coronary intervention derived from CCTA in patients with chronic coronary syndrome.

BACKGROUND: To identify anatomical and morphological plaque features predictors of PCI and create a multiparametric score to increase the predictive yield. Moreover, we assessed the incremental predictive value of FFRCT (Fractional Flow Reserve derived from CCTA) trans-lesion gradient (ΔFFRCT) when integrated into the score. METHODS: Observational cohort study including patients undergoing CCTA for suspected coronary artery disease, with FFRCT available, referred to invasive coronary angiogram and assessment of fractional flow reserve. Plaque analysis was performed using validated semi-automated software. Logistic regression was performed to identify anatomical and morphological plaque features predictive of PCI. Optimal thresholds were defined by area under the receiver-operating characteristics curve (AUC) analysis. A scoring system was developed in a derivation cohort (70 â€‹% of the study population) and tested in a validation cohort (30 â€‹% of patients). RESULTS: The overall study population included 340 patients (455 vessels), among which 238 patients (320 vessels) were included in the derivation cohort. At multivariate logistic regression analysis, absence of left main disease, diameter stenosis (DS), non-calcified plaque (NCP) volume, and percent atheroma volume (PAV) were independent predictors of PCI. Optimal thresholds were: DS â€‹≥ â€‹50 â€‹%, volume of NCP>113 â€‹mm3 and PAV>17 â€‹%. A weighted score (CT-PCI Score) ranging from 0 to 11 was obtained. The AUC of the score was 0.80 (95%CI 0.74-0.86). The integration of ΔFFRCT in the CT-PCI score led to a mild albeit not significant increase in the AUC (0.82, 95%CI 0.77-0.87, p â€‹= â€‹0.328). CONCLUSIONS: Plaque anatomy and morphology derived from CCTA could aid in identifying patients amenable to PCI.

Combined Cardiac Damage Staging by Echocardiography and Cardiac Catheterization in Patients With Clinically Significant Aortic Stenosis.

BACKGROUND: Cardiac damage (CD) staging enhances risk stratification in patients with clinically significant aortic stenosis (AS). We aimed to assess the prognostic value and reclassification rate of right heart catheterization (RHC) compared with transthoracic echocardiography (TTE) in characterising CD staging at 3-year follow-up in patients with clinically significant AS, to identify patients that would benefit from RHC for prognostic stratification, and to test the prognostic value of combined CD staging. METHODS: An observational cohort study of 432 AS patients undergoing TTE and RHC were divided into moderate or asymptomatic severe (m/asAS) and symptomatic severe (ssAS) AS. Kaplan-Meier curves were used to compare survival. The accuracy in prognostic stratification was tested by area under the receiver operating characteristic curve analysis and Delong test. RESULTS: In both cohorts, TTE- and RHC-derived staging systems had prognostic value, although the agreement between them appeared moderate. A higher proportion of patients were assigned to stage 2 by TTE than by RHC. Patients in TTE-derived stage 2 had a high reclassification rate, with 40%-50% presenting with right chamber involvement (stages 3-4) according to RHC. Discordant cases were significantly older, with higher prevalence of atrial fibrillation, markedly elevated N-terminal pro-B-type natriuretic peptide, and higher indexed left atrial volume, E/e', and systolic pulmonary artery pressure vs concordant cases (P < 0.05). The combined CD staging, integrating TTE and RHC, was more accurate in predicting mortality than the TTE-derived system (P < 0.05). CONCLUSIONS: In patients with m/asAS and ssAS, the combined CD staging, derived from TTE and RHC, was more accurate in predicting mortality than TTE alone. In a subset of AS patients, the integration of RHC may significantly improve prognostic stratification.

Obesity in heart failure with preserved ejection fraction: Insights from the REDUCE LAP-HF II trial.

AIMS: Obesity is causally related to the development of heart failure with preserved ejection fraction (HFpEF) but complicates the diagnosis and treatment of this disorder. We aimed to determine the relationship between severity of obesity and clinical, echocardiographic and haemodynamic parameters in a large cohort of patients with documented HFpEF. METHODS AND RESULTS: The REDUCE LAP-HF II trial randomized 626 patients with ejection fraction ≥40% and exercise pulmonary capillary wedge pressure (PCWP) ≥25 mmHg to atrial shunt or sham procedure. We tested for associations between body mass index (BMI), clinical characteristics, cardiac structural and functional abnormalities, physical limitations, quality of life and outcomes with atrial shunt therapy. Overall, 60.9% of patients had BMI ≥30 kg/m2 . As the severity of obesity increased, symptoms (Kansas City Cardiomyopathy Questionnaire score) and 6-min walk distance worsened. More severe obesity was associated with lower natriuretic peptide levels despite more cardiac remodelling, higher cardiac filling pressures, and higher cardiac output. Lower cut points for E/e' were needed to identify elevated PCWP in more obese patients. Strain measurements in all four chambers were maintained as BMI increased. Pulmonary vascular resistance at rest and exercise decreased with higher BMI. Obesity was associated with more first and recurrent heart failure events. However, there was no significant interaction between obesity and treatment effects of the atrial shunt. CONCLUSIONS: Increasing severity of obesity was associated with greater cardiac remodelling, higher right and left ventricular filling pressures, higher cardiac output and increased subsequent heart failure events. Despite significant obesity, many HFpEF patients have preserved right heart and pulmonary vascular function and thus, may be appropriate candidates for atrial shunt therapy.

Impact of coronary CT image quality on the accuracy of the FFRCT Planner.

OBJECTIVE: To assess the accuracy of a virtual stenting tool based on coronary CT angiography (CCTA) and fractional flow reserve (FFR) derived from CCTA (FFRCT Planner) across different levels of image quality. MATERIALS AND METHODS: Prospective, multicenter, single-arm study of patients with chronic coronary syndromes and lesions with FFR ≤ 0.80. All patients underwent CCTA performed with recent-generation scanners. CCTA image quality was adjudicated using the four-point Likert scale at a per-vessel level by an independent committee blinded to the FFRCT Planner. Patient- and technical-related factors that could affect the FFRCT Planner accuracy were evaluated. The FFRCT Planner was applied mirroring percutaneous coronary intervention (PCI) to determine the agreement with invasively measured post-PCI FFR. RESULTS: Overall, 120 patients (123 vessels) were included. Invasive post-PCI FFR was 0.88 ± 0.06 and Planner FFRCT was 0.86 ± 0.06 (mean difference 0.02 FFR units, the lower limit of agreement (LLA) - 0.12, upper limit of agreement (ULA) 0.15). CCTA image quality was assessed as excellent (Likert score 4) in 48.3%, good (Likert score 3) in 45%, and sufficient (Likert score 2) in 6.7% of patients. The FFRCT Planner was accurate across different levels of image quality with a mean difference between FFRCT Planner and invasive post-PCI FFR of 0.02 ± 0.07 in Likert score 4, 0.02 ± 0.07 in Likert score 3 and 0.03 ± 0.08 in Likert score 2, p = 0.695. Nitrate dose ≥ 0.8mg was the only independent factor associated with the accuracy of the FFRCT Planner (95%CI - 0.06 to - 0.001, p = 0.040). CONCLUSION: The FFRCT Planner was accurate in predicting post-PCI FFR independent of CCTA image quality. CLINICAL RELEVANCE STATEMENT: Being accurate in predicting post-PCI FFR across a wide spectrum of CT image quality, the FFRCT Planner could potentially enhance and guide the invasive treatment. Adequate vasodilation during CT acquisition is relevant to improve the accuracy of the FFRCT Planner. KEY POINTS: • The fractional flow reserve derived from coronary CT angiography (FFRCT) Planner is a novel tool able to accurately predict fractional flow reserve after percutaneous coronary intervention. • The accuracy of the FFRCT Planner was confirmed across a wide spectrum of CT image quality. Nitrates dose at CT acquisition was the only independent predictor of its accuracy. • The FFRCT Planner could potentially enhance and guide the invasive treatment.

Coronary Microvascular Dysfunction in Patients With Heart Failure: Characterization of Patterns in HFrEF Versus HFpEF.

BACKGROUND: Coronary microvascular dysfunction (CMD) is involved in heart failure (HF) onset and progression, independently of HF phenotype and obstructive coronary artery disease. Invasive assessment of CMD might provide insights into phenotyping and prognosis of patients with HF. We aimed to assess absolute coronary flow, absolute microvascular resistance, myocardial perfusion, coronary flow reserve, and microvascular resistance reserve in patients with HF with preserved ejection fraction and HF with reduced ejection fraction (HFrEF). METHODS: Single-center, prospective study of 56 consecutive patients with de novo HF with nonobstructive coronary artery disease divided into HF with preserved ejection fraction (n=21) and HFrEF (n=35). CMD was invasively assessed by continuous intracoronary thermodilution and defined as coronary flow reserve <2.5. Left ventricular and left anterior descending artery-related myocardial mass was quantified by echocardiography and coronary computed tomography angiography. Myocardial perfusion (mL/min per g) was calculated as the ratio between absolute coronary flow and left anterior descending artery-related mass. RESULTS: Patients with HFrEF showed a higher left ventricular and left anterior descending artery-related myocardial mass compared with HF with preserved ejection fraction (P<0.010). Overall, 52% of the study population had CMD, with a similar prevalence between the 2 groups. In HFrEF, CMD was characterized by lower absolute microvascular resistance and higher absolute coronary flow at rest (functional CMD; P=0.002). CMD was an independent predictor of a lower rate of left ventricular reverse remodeling at follow-up. In patients with HF with preserved ejection fraction, CMD was mainly due to higher absolute microvascular resistance and lower absolute coronary flow during hyperemia (structural CMD; P≤0.030). CONCLUSIONS: Continuous intracoronary thermodilution allows the definition and characterization of patterns with distinct CMD in patients with HF and could identify patients with HFrEF with a higher rate of left ventricular reverse remodeling at follow-up.

Cardiac Magnetic Resonance Identifies Responders to Cardiac Resynchronization Therapy with an Assessment of Septal Scar and Left Ventricular Dyssynchrony.

Background: The response to cardiac resynchronization therapy (CRT) depends on septal viability and correction of abnormal septal motion. This study investigates if cardiac magnetic resonance (CMR) as a single modality can identify CRT responders with combined imaging of pathological septal motion (septal flash) and septal scar. Methods: In a prospective, multicenter, observational study of 136 CRT recipients, septal scar was assessed using late gadolinium enhancement (LGE) (n = 127) and septal flash visually from cine CMR sequences. The primary endpoint was CRT response, defined as ≥15% reduction in LV end-systolic volume with echocardiography after 6 months. The secondary endpoint was heart transplantation or death of any cause assessed after 39 ± 13 months. Results: Septal scar and septal flash were independent predictors of CRT response in multivariable analysis (both p < 0.001), while QRS duration and morphology were not. The combined approach of septal scar and septal flash predicted CRT response with an area under the curve of 0.86 (95% confidence interval (CI): 0.78-0.94) and was a strong predictor of long-term survival without heart transplantation (hazard ratio 0.27, 95% CI: 0.10-0.79). The accuracy of the approach was similar in the subgroup with intermediate (130-150 ms) QRS duration. The combined approach was superior to septal scar and septal flash alone (p < 0.01). Conclusions: The combined assessment of septal scar and septal flash using CMR as a single-image modality identifies CRT responders with high accuracy and predicts long-term survival.

Association of Mild-to-Moderate Aortic Regurgitation With Outcomes in Heart Failure With Preserved Ejection Fraction.

OBJECTIVE: To assess aortic regurgitation (AR) prevalence, its hemodynamic effect, and long-term prognostic implications in patients admitted with de novo or worsened heart failure with preserved ejection fraction (HFpEF). METHODS: Consecutive patients hospitalized with de novo or worsened HFpEF between 2014 and 2020 were enrolled. Patients with more than moderate aortic and/or mitral valve disease were excluded. Based on the presence and degree of AR, patients were divided into those without AR, those with mild, and those with moderate AR. Data on cardiovascular death, heart failure (HF) rehospitalization, and their composite (major adverse cardiovascular events) were collected. RESULTS: The final study population consisted of 458 HFpEF patients: 156 (34.1%) with mild-AR, 153 (33.4%) with moderate-AR, and the remaining 149 (32.5%) with no AR. Mild-to-moderate AR patients were older, with larger left atrium-left ventricle (LV) volumes, greater LV mass index, higher filling pressure, and prevalence of diastolic dysfunction compared with the no-AR group (all P<.05). During 5-year follow-up, 113 patients died of cardiovascular causes, 124 patients were rehospitalized for HF, whereas 196 experienced the composite endpoint. Mild-to-moderate AR was identified as an independent predictor of all-cause death (HR, 1.62; 95% CI, 1.14 to 1.58; P=.04) and major adverse cardiovascular event occurrence (HR, 1.48; 95% CI, 1.05 to 2.09; P=.02). A total of 126 (35.5%) of 355 patients showed progression of AR at follow-up echocardiography. CONCLUSION: Mild-to-moderate AR is common among patients hospitalized for HFpEF. It is associated with adverse LV remodeling and worse long-term outcomes. These findings warrant further prospective studies addressing the importance of AR in prognostic stratification and exploring therapeutic strategies to mitigate its hemodynamic effect on HF.

Mechanical Dyssynchrony Combined with Septal Scarring Reliably Identifies Responders to Cardiac Resynchronization Therapy.

Background and aim: The presence of mechanical dyssynchrony on echocardiography is associated with reverse remodelling and decreased mortality after cardiac resynchronization therapy (CRT). Contrarily, myocardial scar reduces the effect of CRT. This study investigated how well a combined assessment of different markers of mechanical dyssynchrony and scarring identifies CRT responders. Methods: In a prospective multicentre study of 170 CRT recipients, septal flash (SF), apical rocking (ApRock), systolic stretch index (SSI), and lateral-to-septal (LW-S) work differences were assessed using echocardiography. Myocardial scarring was quantified using cardiac magnetic resonance imaging (CMR) or excluded based on a coronary angiogram and clinical history. The primary endpoint was a CRT response, defined as a ≥15% reduction in LV end-systolic volume 12 months after implantation. The secondary endpoint was time-to-death. Results: The combined assessment of mechanical dyssynchrony and septal scarring showed AUCs ranging between 0.81 (95%CI: 0.74-0.88) and 0.86 (95%CI: 0.79-0.91) for predicting a CRT response, without significant differences between the markers, but significantly higher than mechanical dyssynchrony alone. QRS morphology, QRS duration, and LV ejection fraction were not superior in their prediction. Predictive power was similar in the subgroups of patients with ischemic cardiomyopathy. The combined assessments significantly predicted all-cause mortality at 44 ± 13 months after CRT with a hazard ratio ranging from 0.28 (95%CI: 0.12-0.67) to 0.20 (95%CI: 0.08-0.49). Conclusions: The combined assessment of mechanical dyssynchrony and septal scarring identified CRT responders with high predictive power. Both visual and quantitative markers were highly feasible and demonstrated similar results. This work demonstrates the value of imaging LV mechanics and scarring in CRT candidates, which can already be achieved in a clinical routine.

State-of-the-Art: Noninvasive Assessment of Left Ventricular Function Through Myocardial Work.

The assessment of myocardial work (MW) using noninvasive pressure-strain loop analysis is a novel echocardiographic method that provides a more precise assessment of cardiac performance by considering the left ventricular loading condition. By integrating various MW components such as index, efficiency, and constructive and wasted work, an extensive analysis of left ventricular mechanics and energetics can be achieved. This approach offers a more comprehensive assessment of global cardiac function and performance, surpassing conventional surrogate indices. In this review, we aim to summarize the existing knowledge on MW and its distinctive characteristics in various cardiac pathologies.

Inter-center reproducibility of standard and advanced echocardiographic parameters in the EACVI-AFib echo registry.

AIM: we sought to test the inter-center reproducibility of 16 echo laboratories involved in the EACVI-Afib Echo Europe. METHODS: This was done on a dedicated setting of 10 patients with sinus rhythm (SR) and 10 with persistent atrial fibrillation (AF), collected by the Principal Investigator. Images and loops of echo-exams were stored and made available for labs. The tested measurements included main echo-Doppler parameters, global longitudinal strain (GLS) and peak atrial longitudinal strain (PALS). RESULTS: Single measures interclass correlation coefficients (ICCs) of left ventricular mass and ejection fraction were suboptimal in both patients with SR and AF. Among diastolic parameters, ICCs of deceleration time were poor, in particular in AF (=.50). ICCs of left atrial size and function, besides optimal in AF, showed an acceptable despite moderate concordance in SR. ICC of GLS was .81 and .78 in SR and AF respectively. ICCs of PALS were suitable but lower in 4-chamber than in 2-chamber view. By depicting the boxplot of the 16 laboratories, GLS distribution was completely homogeneous in SR, whereas GLS of AF and PALS of both SR and AF presented a limited number of outliers. GLS mean ± SE of the 16 labs was 19.7 ± .36 (95% CI: 18.8-20.4) in SR and 16.5 ± .29 (95% CI: 15.9-17.1) in AF, whereas PALS mean ± SE was 43.8 ± .70 (95% CI: 42.3-45.3) and 10.2 ± .32 (95% CI: 9.5-10.9) respectively. CONCLUSION: While the utilization of some standard-echo variables should be discouraged in registries, the application of GLS and PALS could be largely promoted because their superior reproducibility, even in AF.

Diagnostic and Prognostic Role of Cardiac Magnetic Resonance in MINOCA: Systematic Review and Meta-Analysis.

BACKGROUND: Myocardial infarction with nonobstructive coronary arteries (MINOCA) is common in current clinical practice. Cardiac magnetic resonance (CMR) plays an important role in its management and is increasingly recommended by all the current guidelines. However, the prognostic value of CMR in patients with MINOCA is still undetermined. OBJECTIVES: The purpose of this study was to determine the diagnostic and prognostic value of CMR in the management of patients with MINOCA. METHODS: A systematic review was performed to identify studies reporting the results of CMR findings in patients with MINOCA. Random effects models were used to determine the prevalence of different disease entities: myocarditis, myocardial infarction (MI), or takotsubo syndrome. Pooled odds ratios (ORs) and 95% CIs were calculated to evaluate the prognostic value of CMR diagnosis in the subgroup of studies that reported clinical outcomes. RESULTS: A total of 26 studies comprising 3,624 patients were included. The mean age was 54.2 ± 5.3 years, and 56% were men. MINOCA was confirmed in only 22% (95% CI: 0.17-0.26) of the cases and 68% of patients with initial MINOCA were reclassified after the CMR assessment. The pooled prevalence of myocarditis was 31% (95% CI: 0.25-0.39), and takotsubo syndrome 10% (95% CI: 0.06-0.12). In a subgroup analysis of 5 studies (770 patients) that reported clinical outcomes, CMR diagnosis of confirmed MI was associated with an increased risk of major adverse cardiovascular events (pooled OR: 2.40; 95% CI: 1.60-3.59). CONCLUSIONS: In patients with MINOCA, CMR has been demonstrated to add an important diagnostic and prognostic value, proving to be crucial for the diagnosis of this condition. Sixty-eight percent of patients with initial MINOCA were reclassified after the CMR evaluation. CMR-confirmed diagnosis of MINOCA was associated with an increased risk of major adverse cardiovascular events at follow-up.

Exercise-Induced Left Atrial Hypertension in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Many patients with heart failure and preserved ejection fraction have no overt volume overload and normal resting left atrial (LA) pressure. OBJECTIVES: This study sought to characterize patients with normal resting LA pressure (pulmonary capillary wedge pressure [PCWP] <15 mm Hg) but exercise-induced left atrial hypertension (EILAH). METHODS: The REDUCE LAP-HF II (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) trial randomized 626 patients with ejection fraction ≥40% and exercise PCWP ≥25 mm Hg to atrial shunt or sham procedure. The primary trial outcome, a hierarchical composite of death, heart failure hospitalization, intensification of diuretics, and change in health status was compared between patients with EILAH and those with heart failure and resting left atrial hypertension (RELAH). RESULTS: Patients with EILAH (29%) had similar symptom severity, but lower natriuretic peptide levels, higher 6-minute walk distance, less atrial fibrillation, lower left ventricular mass, smaller LA volumes, lower E/e', and better LA strain. PCWP was lower at rest, but had a larger increase with exercise in EILAH. Neither group as a whole had a significant effect from shunt therapy vs sham. Patients with EILAH were more likely to have characteristics associated with atrial shunt responsiveness (peak exercise pulmonary vascular resistance <1.74 WU) and no pacemaker (63% vs 46%; P < 0.001). The win ratio for the primary outcome was 1.56 (P = 0.08) in patients with EILAH and 1.51 (P = 0.04) in those with RELAH when responder characteristics were present. CONCLUSIONS: Patients with EILAH had similar symptom severity but less advanced myocardial and pulmonary vascular disease. This important subgroup may be difficult to diagnose without invasive exercise hemodynamics, but it has characteristics associated with favorable response to atrial shunt therapy. (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure [REDUCE LAP-HF TRIAL II]; NCT03088033).