AIMS:Atrial function measured by left atrial strain (LAS) could represent an early marker of disease and poor cardiovascular outcome. Given the importance of identifying early markers of adverse outcome beyond let ventricular ejection fraction (LVEF) and left atrial volume (LAV), our aim was to assess the association of LAS with major cardiovascular events, both in the general population and in specific cardiovascular diseases. METHODS AND RESULTS:We systematically searched PUBMED, COCHRANE Central Register of Controlled Trials and WEB OF SCIENCE (WoS) up to October 2023. Studies were included if they assessed LAS, measured by speckle-tracking echocardiography and analyzed as a continuous variable, and cardiovascular outcome. The primary endpoint was a composite of all-cause death and heart failure (HF) hospitalizations. A meta-analysis following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework was conducted. Sixteen reports including 13156 participants were eligible. LAS predicted outcome in a population with and without a variety of cardiovascular conditions (HR 0.91; 95% CI 0.86-0.96). The result was confirmed in patients with HF (HR, 0.93; 95% CI, 0.89-0.97), IHD (HR, 0.95; 95% CI 0.91-0.99) or VHD (HR, 0.94; 95% CI, 0.90-0.97), but not in patients with LVH (HR, 0.98; 95% CI, 0.84-1.15). The metaregression conducted considering LVEF values as a covariate showed no significant effect on the main effect size. CONCLUSIONS:LAS represents a powerful predictor of major cardiovascular events in the general population and in patients with different cardiovascular diseases across left ventricular ejection fraction (LVEF) ranges.

INTRODUCTION:Tricuspid regurgitation is frequent, and its related systemic venous congestion is associated with mortality. Diuretics are the main therapy but what shapes their effect is not fully known. AIM AND METHODS:In this single-center cross-sectional study, we aimed to assess the association of right heart metrics of size and function in relation to diuretic dose. In consecutive patients with measurable tricuspid regurgitation regurgitant volume (RVol) by echocardiography, a high diuretic dose (HDD) was considered a furosemide dose (or equivalent) of greater than 40 mg. Parameters of right atrial (RA) and right ventricular (RV) size and function, tricuspid regurgitation degree and congestion signs were compared between groups with or without HDD. RESULTS:Of 120 patients (37% men; age 74 ± 13 years), 31.7% had HDD. HDD was prevalent in 16% of patients with mild tricuspid regurgitation, 25% with moderate tricuspid regurgitation and 49% with severe tricuspid regurgitation ( P  = 0.011). In multivariate analysis including RV and RA parameters of size and function, only the RA strain was independently associated with diuretic therapy ( B -0.111, P  < 0.0001) and HDD ( B -0.101, P  = 0.007). There was a progressive decline in RA strain with increasing diuretic dose ( PANOVA  < 0.0001). The RA strain was lower in HDD patients independently of chronic kidney disease ( P for interaction 0.798) and tricuspid regurgitation severity ( P for interaction 0.712). Most patients with congestive signs showed a lower RA strain (all P  < 0.05). CONCLUSION:Reduced RA function in tricuspid regurgitation patients with venous congestion is independently associated with a higher dose of diuretic therapy.

BACKGROUND:In primary mitral regurgitation (MR) atrial dysfunction is believed to be the result of atrial interstitial fibrotic replacement, and left atrial (LA) strain has been suggested as a non-invasive tool to identify a maladaptive atrial remodelling beyond LA enlargement. We aim to investigate the association between LA function and the extent of interstitial fibrosis within the atrial wall in patients undergoing surgery, and their relation with MR characteristics and clinical profiles. METHODS:49 consecutive patients (61 ± 10 years, men 75%) with severe primary MR due to prolapse or flail were enrolled the day before surgery and a complete echocardiographic examination with LA strain analysis was performed. During surgery, a single-site full-thickness sample of the LA free wall was obtained from each patient. RESULTS:Areas of interstitial fibrosis were detected in all atrial specimens (median degree 6.5% [4.75-9.25]). No correlation was found between fibrosis degree and echocardiographic parameters like LA strain, LA volume, quantitative parameters of MR degree, regurgitant jet direction, estimated pulmonary artery pressure (sPAP), or clinical parameters like NYHA class or NTproBNP. However, lower LA reservoir and contractile strain values were associated with higher sPAP (p = 0.002 and p = 0.01, respectively), NTproBNP values (p < 0.0001) and symptoms severity (p < 0.05). CONCLUSIONS:In this selected cohort with severe primary MR and relatively low single-site histological LA fibrosis, LA strain was associated with markers of haemodynamic burden but not with biopsy-derived fibrosis percentage.

Abstract Background tricuspid regurgitation (TR) is frequent, and its related systemic venous congestion is associated with mortality. Purpose This study aims to evaluate the role of right atrial (RA) function, measured using the strain technique, on the medium- to long-term clinical effects of tricuspid regurgitation (TR). Our primary objective was to analyze the impact of RA function, measured at baseline, on a composite endpoint consisting of death and/or hospitalization for predominantly right-sided heart failure. The secondary endpoints are hospitalizations, worsening of renal function, and an increase in diuretic dosage (DD). Methods We performed a single center, prospective, observational study regarding adult patients with tricuspid regurgitation and measurable effective regurgitant orifice area (EROA) and a state of hemodynamic stability that underwent a complete echocardiography and full cardiologic evaluation in our Institution, from January 2020 to February 2023. Those patients with acute HF, poor quality imaging, previous repair or prosthetic replacement of the tricuspid valve, and severe renal or hepatic insufficiency were excluded. Patients were assessed clinically at each follow up. Results 134 patients were included (females 62%, mean age 73 ± 13 years old). Median follow up was 23,5 months (12 - 34 months). TR was functional in 87% of cases and was more than moderate in 52% of cases. Mean RA strain was 18,7 ± 11,2%, and divided patients in low strain (LS) and high strain (HS). HS was associated with lower increase and frequently a decrease in DD (-5,5 ± 44,7 mg vs 20,8 ± 63,2 mg, p = 0,009) but no echocardiographic variable independently predicted an increase in DD. Patients with worsening renal function had significantly lower RA (16.7 ± 10.6% vs 20.7 ± 10.9%, p 0.042). LS independently predicted a worsening renal function (OR 3,07; 95% CI 1,026-9,2). RA strain was significantly lower in hospitalized patients (13.1 ± 8 vs 20.3 ± 11.4, p<0.001). Cox regression analysis showed a LS to be an independent predictor of the composite endpoint (adjusted HR 3.1, 95% CI 1.101 – 8.74) correcting for other clinical and echocardiographic variables. ROC curve analysis showed an RA strain cut-off of 18.5% to have a sensitivity of 79% and specificity of 56% in predicting the combined endpoint. Conclusions RA strain is associated with DD and LS patients have higher DD at follow up. RA strain is an independent predictor of worsening renal function. RA function measured by strain is an independent predictor of the composite endpoint of death and/or hospitalization.

Abstract Introduction breast cancer is the most common cancer among women, and in those undergoing chemotherapy, a potential adverse event is cardiotoxicity. Various clinical scores and echocardiographic parameters have been proposed, but predicting left ventricular dysfunction remains challenging. Purpose this study aims to identify baseline pre-chemotherapy echocardiographic parameters that can predict cardiotoxicity. Methods consecutive patients diagnosed with non-metastatic breast cancer and treated with chemotherapy (including anthracycline, anti-HER2, taxanes or hormonal therapy) were prospectively enrolled and followed for one year with clinical and echocardiographic assessments at baseline and every three months. The diagnosis of cancer therapy-related cardiac dysfunction (CTRCD) was based on the 2022 ESC Guidelines. The case series was therefore divided based on the occurrence of mild CTRCD or not. For descriptive purpose we used mean and confidence intervals; median and interquartile ranges when appropriated. We used Student's T-test or Mann-Whitney U for within-group differences, paired T-test or Wilcoxon-Signed-Rank Test for repeated controls. CTRCD onset over time was evaluated using the Kaplan-Meier method. ROC analysis was used to identify cut-off values able to define at risk patients. Statistical significance was setted at p < 0.05. Results we examined 138 patients with an average age of 53.52 years. 58 patients developed mild CTRCD, (18 within the first trimester, 26 between 3-6 months, 8 between 6-9 months, and 6 between 9-12 months). (Picture 1). Parameters like left ventricle global longitudinal strain (GLS), left ventricle eiection fraction (LVEF), early peak atrial longitudinal strain (PALS), peak atrial contraction (PACS) and left atrial volume were evaluated. These parameters showed significant deterioration over time in the overall population; PACS and PALS changed early at 3 months, but nothing was significantly correlated with mild CTRCD diagnosis. A significant difference between the two groups was observed only for PALS at 6 months and PACS at 12 months. At the ROC analysis only GLS showed clinical utility in predicting mild CTRCD with an AUC of 0.83 (Picture 2), and the best cut-off value was -21 (sensitivity 0.724, specificity 0.850, positive predictive value 0.778, negative predictive value 0.810). Conclusions echocardiographic parameters worsened over time in chemotherapy patients. Atrial strain showed significant differences between groups. Basal atrial parameters did not predict CTRCD in our study, but literature supports the relevance of left atrial strain for predicting CTRCD. A baseline GLS value of ≤ -21 may indicate a higher likelihood of mild cardiotoxicity, probably because chemotherapy effect could cause more easily a reduction > 15% in GLS without reduction in LVEF when the baseline GLS is more negative. These findings require confirmation from larger studies.

Tricuspid regurgitation (TR) is related to survival, and right atrial (RA) size and function may play a role. This study aimed to assess the impact of RA function measured by strain (RA strain [RAS]) on outcome and end-organ congestion. We enrolled 134 patients (mean age 73 ± 13 years, 62% women) with any TR grade or etiology and a complete echocardiogram, clinical follow-up, and renal function assessment. The primary end point was a combination of overall mortality and right-sided heart failure hospitalization, and the secondary end point was worsening renal function (WRF). After a median follow-up of 23.5 months (interquartile range 12 to 34 months), the combined end point was reached by 31% of patients. Patients with RAS ≤18% showed lower event-free survival (log-rank p <0.001). In the multivariable analysis, RAS ≤18% (HR 3.1, 95% CI 1.1 to 8.8) and pulmonary artery systolic pressure (PASP) (hazard ratio [HR] 1.02, 95% confidence interval [CI] 1 to 1.05) were independent predictors of the primary end point. Patients with RAS ≤18% and PASP >45 mm Hg had the worst outcome (HR 4.3, 95% CI 2 to 9.5). RAS ≤18% (odds ratio 3.22, 95% CI 1.11 to 9.33) and PASP >45 mm Hg (OR 3.2, 95% CI 1.15 to 8.88) were independent predictors of WRF, adjusting for TR severity, left and right ventricular function, age, gender, diabetes, diuretics, atrial fibrillation. The addition of RAS ≤18% had incremental power over PASP and echocardiographic variables of TR severity and right or left ventricular function to predict WRF (p = 0.026). In conclusion, RA function measured by RAS independently predicts mortality and hospitalizations in patients with TR and independently and incrementally predicts WRF over time.

Leadless pacemakers as the Medtronic Micra AV, have improved cardiac pacing by reducing complications associated with traditional systems. However, achieving high atrioventricular synchrony (AVS) remains a challenge, especially in patients with a high pacing burden. This prospective study enrolled 30 patients to assess the role of echocardiographic parameters in predicting AVS postimplantation. AVS was evaluated via 24-h Holter monitoring, with a median AVS of 67.9% ± 9.6%. Right atrial function, particularly the tricuspidal E wave deceleration time, emerged as the only independent predictor of AVS (p = 0.03), with an AUC of 0.77. These findings suggest that pre-implantation echocardiographic assessment of right atrial parameters could aid in selecting patients who would benefit most from Micra AV. Further studies with larger cohorts and extended follow-ups are warranted.

Coronary angiography (CA) is poorly correlated with non-invasive myocardial stress imaging (NSI) and myocardial ischemia is often observed in patients with unobstructed coronary arteries. Moreover, the diagnostic performance of combined epicardial and microcirculatory angiography-derived physiological assessment and its correlation with NSI remains unknown. A total of 917 coronary vessels in 319 patients who underwent both CA and NSI were included in this multicenter observational retrospective analysis. Quantitative flow ratio (QFR) and angiography-derived index of microcirculatory resistance (IMRangio) analyses were performed to estimate coronary epicardial and microcirculatory function respectively. NSI demonstrated evidence of myocardial ischemia in 76% of the cases. IMRangio (36 [22 to 50] vs 29 [21 to 41], p <0.001) was significantly higher and QFR (0.92 [0.78 to 0.99] vs 0.97 [0.91 to 0.99], p <0.001) was significantly lower in vessels subtending ischemic territories. Overall, the diagnostic accuracy of QFR was moderate (area under the curve of receiver operating characteristic [AUC(ROC)] 0.632 [95% confidence interval [CI] 0.589 to 0.674], p <0.0001) but it was higher in patients with normal microcirculatory function (AUC(RO)C = 0.726 [95% CI 0.669 to 0.784], p <0.0001, p Value for AUC(ROC) comparison = 0.009). Combined QFR/IMRangio assessment provided incremental diagnostic performance compared with the evaluation of epicardial or microcirculatory districts in isolation (p Value for AUC comparison <0.0001) and it was able to identify the predominant mechanism of myocardial ischemia in 77% of the patients with positive NSI. Our study suggests the value of a combined angiography-derived assessment of epicardial and microvascular function for the definition of the predominant mechanism of myocardial ischemia in patients with suspected coronary artery disease.

Trastuzumab is widely used in HER2 breast cancer. However, it may cause left ventricular (LV) dysfunction. A decrease in LV global longitudinal strain (GLS) has been previously demonstrated to be a good predictor of subsequent cancer therapy related dysfunction (CTRCD). Left atrial morphological remodeling during Trastuzumab therapy has also been shown. The aim of this study is exploring the relationship between early changes in left atrial function and the development of Trastuzumab-induced cardiotoxicity. Consecutive patients with diagnosis of HER2+non-metastatic breast cancer treated with Trastuzumab were prospectively enrolled. A clinical, conventional, and advanced echocardiographic assessment was performed at baseline and every three months, until a one-year follow-up was reached. One-hundred-sixteen patients completed the 12 months follow-up, 10 (9%) cases of CTRCD were observed, all after the sixth month. GLS and LVEF significantly decreased in the CTRCD group at 6 months of follow-up, with an earlier (3 months) significant worsening in left atrial morpho-functional parameters. Systolic blood pressure, early peak atrial longitudinal strain (PALS), peak atrial contraction (PACS) and left atrial volume (LAVI) changes resulted independent predictors of CTRCD at multivariable logistic regression analysis. Moreover, early changes in PALS and PACS resulted good predictors of CTRCD development (AUC 0.85; p = 0.008, p < 0.001 and 0.77; p = 0.008, respectively). This prospective study emphasizes that the decline in PALS and PACS among trastuzumab-treated patients could possibly increase the accuracy in identifying future CTRCD in non-metastatic HER2 breast cancer cases, adding predictive value to conventional echocardiographic assessment.

Background and aims: Epidemiology of tricuspid regurgitation (TR) is poorly known and its burden in the community is challenging to define. We aimed to evaluate the prevalence of TR in a geographically defined area and its outcome, in particular overall survival and hospitalization, considering different clinical contexts. Methods: We retrospectively analyzed consecutive outpatients referred between 2006 and 2013 for echocardi-ography and clinical evaluation. Patients with at least moderate TR were included and five different clinical settings were defined: concomitant significant left-sided valvular heart disease (LVHD-TR), heart failure (HF-TR), previous open-heart valvular surgery (postop-TR), pulmonary hypertension (PHTN-TR) and isolated TR (iso-lated-TR). Primary endpoint was a composite outcome of all-cause mortality or first hospitalization for HF.Results: Of 6797 consecutive patients with a clinical visit and echocardiograms performed in routine practice in a geographically defined community, moderate or severe TR was found in 4.8% of patients (327) . During median follow-up of 6.1 years, TR severity was a determinant of event-free survival. Analyzed for each clinical subset, eight-year event-free survival was 87 +/- 7% for postop-TR subgroup, 75 +/- 7% for isolated-TR, 67 +/- 6% for PHTN-TR, 58 +/- 6% for LHVD-TR and 52 +/- 11% for HF-TR.Conclusion: Moderate or more TR is a notable finding in the community and has impact on event-free survival in all clinical settings, with the worst outcomes when associated with relevant left-sided valvular heart disease and HF.

Background: By the framework of proportionate/disproportionate secondary mitral regurgitation (sMR), disproportionate sMR is characterized by a low left ventricular stroke volume (SV) and an out of proportion regurgitant fraction (RF) for the same effective regurgitant orifice area (EROA). The degree of aortic stiffness is a determinant of the ventricular forward SV. We aim to analyze the importance of aortic stiffness in influencing the discrepancy between measures of mitral valve lesion severity (EROA) and sMR hemodynamic burden (regurgitant volume [RV] and RF).Methods: We enrolled stable patients with heart failure with reduced ejection fraction (HFrEF) and at least mild sMR. Mitral EROA, RV, RF and aortic pulse wave velocity (PWV) were measured by echocardiography. We defined three groups based on the degree of actual RF deviation from RF estimated by the linear regression equation of RF on EROA (concordant, low-discordant [residuals lower-than -5%] and high-discordant RF [residuals higher-than 5%]). Results: 117 patients were analyzed (68 +/- 13 years; female 30%; LVEF 33 +/- 8%; EROA 16 +/- 12mm2; RV 24 +/- 15 ml; RF 27 +/- 13%; PWV 6.6 +/- 3.2 m/s). LVEF, end-diastolic-volume and EROA didn't differ among groups. PWV and RV were higher in patients with high-discordant RF (p <= 0.01), whereas total left ventricular-SV and left ventricular outflow tract-SV (LVOT-SV) were lower (p <= 0.0004). PWV was associated with LVOT-SV (r=-0.3;p = 0.0008) and RV (r = 0.3;p = 0.0009). High-discordant RF was predicted by PWV (p = 0.001) independently of LVOT-SV and RV.Conclusion: In this HFrEF cohort with sMR, higher PWV was associated with higher-than-expected RF for a given EROA. Aortic stiffness might play a role in the discrepancy between mitral valve lesion severity and sMR hemodynamic burden.

In this work, we performed a computational image-based study of blood dynamics in the whole left heart, both in a healthy subject and in a patient with mitral valve regurgitation. We elaborated multi-series cine-MRI with the aim of reconstructing the geometry and the corresponding motion of left ventricle, left atrium, mitral and aortic valves, and aortic root of the subjects. This allowed us to prescribe such motion to computational blood dynamics simulations where, for the first time, the whole left heart motion of the subject is considered, allowing us to obtain reliable subject-specific information. The final aim is to investigate and compare between the subjects the occurrence of turbulence and the risk of hemolysis and of thrombi formation. In particular, we modeled blood with the Navier–Stokes equations in the arbitrary Lagrangian–Eulerian framework, with a large eddy simulation model to describe the transition to turbulence and a resistive method to manage the valve dynamics, and we used a finite element discretization implemented in an in-house code for the numerical solution.

Tricuspid regurgitation (TR) is a frequent valvular pathology and when significant, may cause systemic venous congestion (SC). The right atrium (RA) is an intermediate structure between the tricuspid valve and the venous system and its role in SC is not yet defined. A total of 116 patients with a measurable TR effective regurgitant orifice area (EROA) and regurgitant volume (RVol) were selected from 2020 to 2022. SC was estimated by echocardiography using inferior vena cava diameter and estimated right atrial pressure (eRAP) and by clinical congestive features. TR grade was mild in 23 patients (20%), moderate in 53 patients (46%), and severe in 40 patients (34%). There was a significant decrease in RA function measured by strain with increasing TR severity (p <0.001). There was a marked difference in RA strain between the groups with eRAP >10 and ≤10 mm Hg (25 ± 11% vs 11 ± 7%, p <0.0001). Variables independently associated with inferior vena cava diameter were RA strain (β -0.532, p <0.001), RA volume indexed (β 0.249, p = 0.002), RVol (β 0.229, p = 0.005) and EROA (β 0.185, p = 0.016), and independently associated with eRAP >10 mm Hg were EROA (odds ratio [OR] 1.024, 95% confidence interval [CI] 1.002 to 1.046), RVol (OR 1.039, 95% CI 1.007 to 1.072) and RA strain (OR 0.863, 95% CI 0.794 to 0.940). The addition of RA strain to models containing EROA or RVol significantly improved the power of the model. RA strain was independently associated with the presence of 3 or more congestive features. In conclusion, echocardiographic and clinical signs of SC are frequent in higher degrees of TR, and RA function seems to play a key role in modulating the downstream effect of TR.

Background: Diastolic dysfunction (DD) assessment in heart failure is still challenging. Peak atrial longitudinal strain (PALS) is strongly related to end-diastolic pressure and prognosis, but it is still not part of standard DD assessment. We tested the hypothesis that a machine learning approach would be useful to include PALS in DD classification and refine prognostic stratification. Methods: In a derivation cohort of 864 heart failure patients in sinus rhythm (age, 66.6±12 years; heart failure with reduced ejection fraction, n=541; heart failure with mildly reduced ejection fraction, n=129; heart failure with preserved ejection fraction, n=194), machine learning techniques were retrospectively applied to PALS and guideline-recommended diastolic variables. Outcome (death/heart failure rehospitalization) of the identified DD-clusters was compared with that by guidelines-based classification. To identify the best combination of variables able to classify patients in one of the identified DD-clusters, classification and regression tree analysis was applied (with DD-clusters as dependent variable and PALS plus guidelines-recommended diastolic variables as explanatory variables). The algorithm was subsequently validated in a prospective cohort of 189 heart failure outpatients (age, 65±13 years). Results: Three distinct echocardiographic DD-clusters were identified (cluster-1, n=212; cluster-2, n=376; cluster-3 DD, n=276), with modest agreement with guidelines-recommended classification (kappa=0.40; P <0.001). DD-clusters were predicted by a simple algorithm including E/A ratio, left atrial volume index, E/e′ ratio, and PALS. After 36.5±29.4 months follow-up, 318 events occurred. Compared to guideline-based classification, DD-clusters showed a better association with events in multivariable models (C-index 0.720 versus 0.733, P =0.033; net reclassification improvement 0.166 [95% CI, 0.035–0.276], P =0.013), without interaction with ejection fraction category. In the validation cohort (median follow-up: 18.5 months), cluster-based classification better predicted outcome than guideline-based classification (C-index 0.80 versus 0.78, P =0.093). Conclusions: Integrating PALS by machine learning algorithm in DD classification improves risk stratification over recommended current criteria, regardless of ejection fraction status. This proof of concept study needs further validation of the proposed algorithm to assess generalizability to other populations.

HomeJournal of the American Heart AssociationAhead of PrintSensitivity and Specificity of Transthoracic Echocardiography in Diagnosing the Presence of the Anomalous Origin of Left Circumflex Coronary Artery From the Right Sinus of Valsalva in an Adult Population Open AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citations ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toOpen AccessLetterPDF/EPUBSensitivity and Specificity of Transthoracic Echocardiography in Diagnosing the Presence of the Anomalous Origin of Left Circumflex Coronary Artery From the Right Sinus of Valsalva in an Adult Population Stefano Bonapace, Laura Lanzoni, Andrea Rossi, Carmelo Cicciò, Mariantonietta Cicoira, Clementina Dugo, Caterina Maffeis, Filippo Valbusa, Guido Canali, Massimo Guerriero and Giulio Molon Stefano BonapaceStefano Bonapace *Correspondence to: Stefano Bonapace, MD, Division of Cardiology, Istituto di Ricovero e Cura a Carattere Scientifico Sacro Cuore–Don Calabria, via Don Sempreboni 5, 37024 Negrar, Italy. Email: E-mail Address: [email protected] https://orcid.org/0000-0001-9122-2642 , Division of Cardiology, , Istituto di Ricovero e Cura a Carattere Scientifico Sacro Cuore–Don Calabria, , Negrar, , Italy, , Laura LanzoniLaura Lanzoni , Division of Cardiology, , Istituto di Ricovero e Cura a Carattere Scientifico Sacro Cuore–Don Calabria, , Negrar, , Italy, , Andrea RossiAndrea Rossi https://orcid.org/0000-0001-7095-7121 , Division of Cardiology, Department of Medicine, , University of Verona, , Verona, , Italy, , Carmelo CicciòCarmelo Cicciò https://orcid.org/0000-0001-9769-8043 , Division of Radiology, Department of Imaging, , Istituto di Ricovero e Cura a Carattere Scientifico Sacro Cuore–Don Calabria, , Negrar, , Italy, , Mariantonietta CicoiraMariantonietta Cicoira , Division of Cardiolgy, , Ospedale Magalini, , Villafranca, , Italy, , Clementina DugoClementina Dugo https://orcid.org/0000-0002-1457-4975 , Division of Cardiology, , Istituto di Ricovero e Cura a Carattere Scientifico Sacro Cuore–Don Calabria, , Negrar, , Italy, , Caterina MaffeisCaterina Maffeis , Division of Cardiology, Department of Medicine, , University of Verona, , Verona, , Italy, , Filippo ValbusaFilippo Valbusa https://orcid.org/0000-0001-7527-6974 , Division of Internal Medicine, , Istituto di Ricovero e Cura a Carattere Scientifico Sacro Cuore–Don Calabria, , Negrar, , Italy, , Guido CanaliGuido Canali , Division of Cardiology, , Istituto di Ricovero e Cura a Carattere Scientifico Sacro Cuore–Don Calabria, , Negrar, , Italy, , Massimo GuerrieroMassimo Guerriero https://orcid.org/0000-0003-1310-539X , Clinical Research Unit, , Istituto di Ricovero e Cura a Carattere Scientifico Sacro Cuore–Don Calabria, , Negrar, , Italy, and Giulio MolonGiulio Molon , Division of Cardiology, , Istituto di Ricovero e Cura a Carattere Scientifico Sacro Cuore–Don Calabria, , Negrar, , Italy, Originally published29 Jun 2023https://doi.org/10.1161/JAHA.123.030173Journal of the American Heart Association. 2023;0:e030173Anomalous coronary artery (ACA) origin affects around 0.6% to 1.2% of the general population without other congenital heart disease.1 A multimodality imaging approach is usually necessary to correctly assess the origin and proximal course of ACA, and transthoracic echocardiography (TTE) represents the first step in this diagnostic process, followed by coronary computed tomography.1 The anomalous origin of the left circumflex coronary artery (aLCX) from the right coronary sinus, first described by Antopol and Kugel2 in 1933, is the most common ACA, with a prevalence at coronary angiography of 0.18% to 0.67%; 3 different variants are described3: type I with separated ostia between right coronary artery and aLCX (Figure [A]), type II with a common ostium between right coronary artery and aLCX (Figure [B]), and type III with aLCX arising as a proximal branch of right coronary artery with a short common trunk (Figure [C]). Although it is considered a "benign" variant,3 its recognition is useful to avoid its damage during aortic and mitral valve surgical replacement.4 The aim of this observational prospective study was to evaluate the sensitivity and specificity of a TTE sign of a "double binary tubular image" (DBTI; Figure [D–F]), observed above the mitral annular plane and crossing the aorta in apical projections, in predicting the presence of aLCX,5 in all consecutive adult patients (aged >18 years) who underwent TTE before clinically indicated elective coronary angiography between January 2016 and October 2021 at our institution. Angiographic calcifications and the reference vessel diameter with quantitative coronary analysis of aLCX in its retroaortic segment were also assessed. The study protocol was approved by the Ethics Committee of Verona and Rovigo (protocol number 11 568), and all patients provided informed consent. The data of the study may be available from the corresponding author on request. Data are presented as mean±SD or percentage. Unpaired Student t test was used to test differences between continuous variables. Sensitivity was calculated as [true positive (TP)/TP+false negative (FN)]×100, specificity as [true negative (TN)/false positive (FP)+TN]×100, positive predictive value as [TP/TP+FP]×100, negative predictive value as [TN/TN+FN]×100, and the diagnostic accuracy as [TP+TN/TP+TN+FP+FN]×100. A total of 4045 patients, aged 69.9±11.3 years, 72.1% men, were studied. A total of 47 (1.16%) ACA origins were found at coronary angiography, among them 24 (0.59%) had aLCX, 6 (25%) type I, 9 (37.5%) type II, and 9 (37.5%) type III. The mean age of patients with aLCX was 66.1±11.4 years, ranging between 41 and 80 years, and 75% were men. Furthermore, we found 8 (0.19%) anomalous origin of right coronary artery (6 with high take off from the ascending aorta, and 2 originating from the left coronary sinus), 12 (0.29%) absence of left main trunk with split left anterior descending artery and left circumflex coronary artery origin at left coronary sinus, 2 (0.05%) anomalous origin of left anterior descending artery at the right coronary sinus, and 1 (0.02%) single coronary artery arising from right coronary sinus. The DBTI was present in 22 patients at TTE. In 20 of them, the diagnosis was confirmed by coronary angiography; 4 FN and 2 FP subjects were found (Figure [G]).Download figureDownload PowerPointFigure 1. Angiographic appearance of type I, II, and III anomalous origin of the left circumflex coronary artery (aLCX) (A–C; white arrows), the double binary tubular image (DBTI) at transthoracic echocardiography (TTE) in apical 4‐, 5‐, and 2‐chamber views (D–F; white arrows), and the numbers of patients cross‐classified by diagnosis (G).The sensitivity, specificity, positive predictive value, and negative predictive value of this TTE sign were 83.3% (95% CI, –068.4%–98.2%), 99.9% (95% CI, –99.8%–100%), 90.9% (95% CI, –78.9%–102.9%), and 99.9% (95% CI, –99.8%–99.9%), respectively, with a diagnostic accuracy of 99.8%. Among those patients with the DBTI sign, 41.6% had no angiographic calcifications and 58.4% had various degrees of angiographic calcifications. Mild angiographic calcifications were present in 75% among those in whom the DBTI was not identified. There was a significant difference in aLCX retroaortic diameter among those with DBTI compared with those without DBTI (2.53±0.2 versus 1.44±0.14 mm; P<0.0001).This is the first report evaluating the diagnostic accuracy of this TTE sign in predicting the presence of aLCX. Different from other ACA origins in aLCX, TTE was unable to detect the anomalous position of the coronary ostium but allowed us to highlight the retroaortic course of the artery in proceeding from its origin to reach the normal location at the level of the atrioventricular groove.5 This anomalous pathway probably exposes the vessel wall to a more favorable incident ultrasound beam angle (ie, more perpendicular), allowing the best visualization of aLCX during its course rather than at its origin.5 The retroaortic diameter of aLCX rather than its degree of calcifications seems to be the most relevant factor allowing its detection.The main limitation of the study is related to the small number of aLCX, which widens the CI around the estimate of sensitivity, reducing its precision.In conclusion, this study shows, for the first time, that TTE has a high diagnostic accuracy to identify the aLCX in an adult population. The recognition of this DBTI sign at TTE allows us to avoid more invasive and expensive investigations, such as coronary computed tomography scan, for this specific coronary anomaly.Sources of FundingNone.DisclosuresNone.Footnotes*Correspondence to: Stefano Bonapace, MD, Division of Cardiology, Istituto di Ricovero e Cura a Carattere Scientifico Sacro Cuore–Don Calabria, via Don Sempreboni 5, 37024 Negrar, Italy. Email: stefano.[email protected]itThis article was sent to Erik B. Schelbert, MD, MS, Associate Editor, for review by expert referees, editorial decision, and final disposition.For Sources of Funding and Disclosures, see page 3.References1 Angelini P. Coronary artery anomalies. An entity in search of an identity. Circulation. 2007; 10:1296–1305. doi: 10.1161/CIRCULATIONAHA.106.618082LinkGoogle Scholar2 Antopol W, Kugel MA. Anomalous origin of the left circumflex artery. Am Heart J. 1933; 8:802–806. doi: 10.1016/S0002-8703(33)90141-6CrossrefGoogle Scholar3 Page HL, Engel HJ, Campbell WB, Thomas CS. Anomalous origin of the left circumflex coronary artery: recognition, angiographic demonstration and clinical significance. Circulation. 1974; 50:768–773. doi: 10.1161/01.CIR.50.4.768LinkGoogle Scholar4 Vaishnava P, Pyo R, Filsoufi F, Sharma S. Compression of an anomalous left circumflex artery after aortic and mitral valve replacement. Ann Thorac Surg. 2011; 92:1887–1889. doi: 10.1016/j.athoracsur.2011.04.095CrossrefMedlineGoogle Scholar5 Bonapace S, Adamo E, Cicciò C, Chiampan A, Canali G, Valbusa F. Unusual echocardiographic image of a left circumflex coronary artery with anomalous origin from the right coronary sinus. Eur Heart J. 2016; 37:792. doi: 10.1093/eurheartj/ehv341CrossrefMedlineGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. 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Published on behalf of the American Heart Association, Inc., by Wiley BlackwellThis is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.https://doi.org/10.1161/JAHA.123.030173PMID: 37382112 Manuscript receivedMarch 27, 2023Manuscript acceptedJune 9, 2023Originally publishedJune 29, 2023 Keywordsspecificityechocardiographyanomalous coronary arterysensibilityanomalous left circumflex coronary arteryPDF download SubjectsAngiographyDiagnostic TestingEchocardiographyImaging

Myocardial perfusion single photon emission computed tomography (SPECT) is widely used in assessing coronary artery disease (CAD) owing to its proven efficacy in extensive clinical experience. Like other functional tests, myocardial SPECT is recommended for the diagnosis of obstructive CAD, risk stratification assessment, and treatment decision making. Besides quantifying left ventricular volume, global and regional function by electrocardiography (ECG)-gated acquisition, myocardial SPECT can identify myocardial ischemia, scars, stunning, and viable hibernating myocardium. It provides comprehensive functional data across the spectrum of CAD and a cost-effective strategy in patients with intermediate pre-test probability of CAD or with a history of ischemic cardiomyopathy. With ongoing advances in cardiovascular prevention and risk factor management many patients referred for testing now have a low-to-intermediate probability of CAD. Besides, CAD has become a chronic condition resulting from novel therapeutic strategies. Against this background, approaches combining anatomical and functional tests in sequence or simultaneously include coronary artery calcium score integrated with perfusion imaging or fusion SPECT/coronary computed tomography angiography (CCTA). In this review we summarize current indications for myocardial perfusion SPECT and integration of SPECT with other imaging techniques to improve diagnostic performance, patient management, and outcome prediction in CAD.

ABSTRACT In this work we performed a computational image-based study of blood dynamics in the whole left heart, both in a healthy subject and in a patient with mitral valve regurgitation (MVR). We elaborated dynamic cine-MRI images with the aim of reconstructing the geometry and the corresponding motion of left ventricle, left atrium, mitral and aortic valves, and aortic root of the subjects. This allowed us to prescribe such motion to computational blood dynamics simulations where, for the first time, the whole left heart motion of the subject is considered, allowing us to obtain reliable subject-specific information. The final aim is to investigate and compare between the subjects the occurrence of turbulence and the risk of hemolysis and of thrombi formation. In particular, we modeled blood with the Navier-Stokes equations in the Arbitrary Lagrangian-Eulerian framework, with a Large Eddy Simulation model to describe the transition to turbulence and a resistive method to manage the valve dynamics, and we used a Finite Elements discretization implemented in an in-house code for the numerical solution. Our results highlighted that the regurgitant jet in the MVR case gave rise to a large amount of transition to turbulence in the left atrium resulting in a higher risk of formation of hemolysis. Moreover, MVR promoted a more complete washout of stagnant fiows in the left atrium during the systolic phase and in the left ventricle apex during diastole. NEW & NOTEWORTHY Reconstruction from cine-MRI images of geometries and motion of the left heart (left atrium and ventricle, aortic root, aortic and mitral valve) of a healthy and mitral regurgitant patient. Prescription of such motion to a complete subject-specific computational fluid-dynamic simulation of the left heart. Investigation of turbulence in a regurgitant scenario. Study of the mechanisms of prevention from stagnant flows and hemolysis formation in the atrium.

Abstract Background Trastuzumab (TZ) is widely used for his key role in HER2 positive breast cancer. However, the most concerning cardiovascular complication is cardiotoxicity. Many studies have highlighted the importance of screening for subclinical myocardial dysfunction using left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). However, there are only few studies investigating a possible atrial damage. Purpose Aim of this study was to analyze the modification peak atrial systolic longitudinal strain (PALS) in patients undergoing therapy with TZ in a follow-up period of 12 months. The fluctuation of left atrial function parameters under chemotherapy was evaluated focusing the attention on those patients who developed cancer therapy–related cardiac dysfunction (CTRCD). Methods 116 women affected by breast cancer treated with TZ were enrolled. Each patient underwent a complete echocardiography at baseline and every 3 months. Exclusion criteria were poor quality imaging and lack of a complete follow up with consequent missing data. CTRCD was defined as a decrease in the left ventricular ejection fraction of >10 percentage points to a value <53% at any time of follow-up. 2D-Speckle tracking analysis was performed at baseline and at each examination using Tomtec software to analyze both atrial and left ventricular function. Trends of GLS, and PALS during 12 months-follow up periods were analyzed. Additionally, we explored if diabetes and renal impairment were associated with more prevalent atrial subclinical disfunction as demonstrated in previous studies. Results A total of 10 patients (9%) developed cancer therapy–related cardiac dysfunction. A significant reduction in GLS compared to the baseline was observed during the whole follow-up (p=0.05), starting in the first six months of treatment (-21 ± 2% vs -17 ± 2%, p= 0.021). Interestingly, PALS showed a similar trend with a significant decrease during the whole 12 months-follow up (p=0.012), starting in the first 3 months (45 ± 9% vs 35 ± 8%, p=0.001). 6 patients presented a diagnosis of diabetes at baseline, and presented lower PALS compared to the non-diabetic counterpart (38± 10% vs 49 ± 12% p=0.03). 2 patients presented a significant renal impairment (eGFR ≤30 ml/min). Similarly, these patients presented a lower PALS at baseline (32 ± 7% and 48 ± 7%; p=0.055). Conclusions In patients treated with Trastuzumab the development of left atrial impairment is frequent and PALS modifications seem to precede GLS variations in patients with CTRCD, suggesting a possible cardiotoxic effect of such therapy on both atrial and left ventricular myocardium and physiology.

This editorial refers to ‘Transvalvular jet velocity, aortic valve area, mortality and cardiovascular outcomes’, by B. Alcón et al., pp. 601--612. Aortic valve stenosis (AS) represents a relevant cause of morbidity and mortality worldwide. Aortic valve replacement is given to patients with severe symptomatic AS, when the disease strongly affects heart failure symptoms and risk of death. The disease relative risk is regarded as low when the stenosis is less-than-severe, but such benign nature of mild to moderate AS has been recently challenged. The study by Alcón et al. published in this issue of the EHJ-Cardiovascular Imaging1 analysed the outcomes over 5 years of a large, unselected population with any degree of AS and found that the risk increases in parallel to the outflow obstruction degree, but it is already apparent in patients with mild AS, long before it reaches hemodynamic severity. One of the most original...

Abstract Aims We hypothesized that left atrial (LA) remodelling and function are associated with poor exercise capacity as prognostic marker in chronic heart failure (CHF) across a broad range of left ventricular ejection fraction (LVEF). Methods and results One hundred seventy‐one patients with CHF were analysed [age 65 ± 11 years, 136 males (80%); 86 heart failure with reduced ejection fraction (HFrEF), 27 heart failure with mid‐range ejection fraction (HFmrEF), 58 heart failure with preserved ejection fraction (HFpEF)]. All patients underwent echocardiography and maximal cardiopulmonary exercise testing and were classified according to a prognostic cut‐off of peak VO2 (pVO2; 14 mL/kg/min). Seventy‐seven (45%) patients reached pVO2 < 14 and 94 (55%) pVO2 ≥ 14 mL/kg/min. Between the two groups, there was a considerable difference in both left atrial volume (LAVi, 53 ± 24 vs. 44 ± 18 mL/m2, P = 0.005) and function (LA reservoir strain 12 ± 5 vs. 20 ± 10%, P < 0.0001). Receiver‐operating characteristic curves identified LA reservoir strain (area under the curve: 0.73 [0.65–0.80], P < 0.0001) as strong predictor for impaired pVO2 among all echocardiographic variables; LA reservoir strain < 23% had 37% specificity but a very high sensitivity (96%) in identifying a severely reduced pVO2. In logistic regression analysis, LA reservoir strain < 23% was associated with a highly increased risk of pVO2 < 14 mL/kg/min (odds ratio 16.0 [4.7–54.6]; P < 0.0001). The multivariate analysis showed that a reduced LA reservoir strain was associated with pVO2 < 14 mL/kg/min after adjustment for age, body mass index (BMI), and clinical variables, that is, New York Heart Association class, atrial fibrillation, haemoglobin, and creatinine (b 0.22 [95% confidence interval, CI, 0.12–0.31]; P < 0.0001), and after adjustment for echocardiographic variables, that is, LVEF or left ventricular global longitudinal strain (LVGLS) and tricuspid annular plane systolic excursion (TAPSE) (b 0.16 [95% CI 0.08–0.24]; P < 0.0001). Patients with HFrEF, HFmrEF, and HFpEF were separately analysed. Among LA reservoir strain, LAVi, LVEF, LVGLS, and TAPSE, LA reservoir strain was the only one significantly associated with pVO2 in all subgroups (after adjustment for sex and BMI, P = 0.003, 0.04, and 0.01, respectively). Conclusions In patients with CHF, an impaired LA reservoir function is independently associated with a severely reduced pVO2. LA dysfunction represents a marker of poor prognosis across LVEF borders in the CHF population.