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Aim PARADISE-MI examined the efficacy of sacubitril/valsartan in acute myocardial infarction (AMI) complicated by reduced left ventricular ejection fraction (LVEF), pulmonary congestion, or both. We sought to assess the trajectory of pulmonary congestion using lung ultrasound (LUS) and its association with cardiac structure and function in a pre-specified substudy. Methods and results Patients without prior heart failure (HF) underwent eight-zone LUS and echocardiography at baseline (±2 days of randomization) and after 8 months. B-lines were quantified offline, blinded to treatment, clinical findings, time point, and outcomes. Among 152 patients (median age 65, 32% women, mean LVEF 41%), B-lines were detectable in 87% at baseline [median B-line count: 4 (interquartile range 2–8)]. Among 115 patients with LUS data at baseline and follow-up, B-lines decreased significantly from baseline (mean ± standard deviation: −1.6 ± 7.3; P = 0.018). The proportion of patients without pulmonary congestion at follow-up was significantly higher in those with fewer B-lines at baseline. Adjusted for baseline, B-lines at follow-up were on average 6 (95% confidence interval: 3–9) higher in patients who experienced an intercurrent HF event vs. those who did not (P = 0.001). A greater number of B-lines at baseline was associated with larger left atrial size, higher E/e′ and E/A ratios, greater degree of mitral regurgitation, worse right ventricular systolic function, and higher tricuspid regurgitation velocity (P-trend Conclusion In this AMI cohort, B-lines, indicating pulmonary congestion, were common at baseline and, on average, decreased significantly from baseline to follow-up. Worse pulmonary congestion was associated with prognostically important echocardiographic markers.

Aims Hypertensive heart disease (HHD) is recognized as a key clinical precursor to heart failure with preserved ejection fraction (HFPEF). However, pathophysiological transition from HHD to HFPEF is not well understood. We sought determine whether regional differences in impaired myocardial function may underlie the greater mechanical dysfunction seen in HFPEF compared to HHD. Methods and results We used standardized echocardiography to assess regional myocardial deformation in a cohort of n = 327 adults with preserved left ventricular (LV) ejection fraction (≥45%), including: n = 129 with HFPEF, n = 158 with HHD and no heart failure, and n = 40 normotensive controls. From detailed measurements of LV systolic strain performed in multiple views, we derived and then compared regional measures of basal, mid-ventricular, and apical longitudinal strains. In models adjusting for clinical covariates, basal and mid-ventricular LV myocardial deformation was more impaired in HHD than in controls (P ≤ 0.003), whereas apical deformation was more impaired in HFPEF than in HHD (P = 0.005). In multivariable-adjusted analyses, only apical strain remained independently associated with HFPEF vs. HHD status [odds ratio 1.18 (1.02–1.37), P = 0.030 per 1% decrease in apical strain]. Compared to other regional strains, apical longitudinal strain optimally differentiated HFPEF from HHD (area under the receiver operating curve: apical longitudinal strain = 0.67; mid-ventricular longitudinal strain = 0.59; basal longitudinal strain = 0.60). Conclusion We found that while apical mechanical function is preserved in HHD, it was impaired in HFPEF and may contribute to the transition from an asymptomatic heart disease to a symptomatic heart disease.

Background Placement of an interatrial shunt device reduces pulmonary capillary wedge pressure during exercise in patients with heart failure and preserved or mildly reduced ejection fraction. We aimed to investigate whether an interatrial shunt can reduce heart failure events or improve health status in these patients.Methods In this randomised, international, blinded, sham-controlled trial performed at 89 health-care centres, we included patients (aged >= 40 years) with symptomatic heart failure, an ejection fraction of at least 40%, and pulmonary capillary wedge pressure during exercise of at least 25 mm Hg while exceeding right atrial pressure by at least 5 mm Hg. Patients were randomly assigned (1:1) to receive either a shunt device or sham procedure. Patients and outcome assessors were masked to randomisation. The primary endpoint was a hierarchical composite of cardiovascular death or non-fatal ischemic stroke at 12 months, rate of total heart failure events up to 24 months, and change in Kansas City Cardiomyopathy Questionnaire overall summary score at 12 months. Pre-specified subgroup analyses were conducted for the heart failure event endpoint. Analysis of the primary endpoint, all other efficacy endpoints, and safety endpoints was conducted in the modified intention-to-treat population, defined as all patients randomly allocated to receive treatment, excluding those found to be ineligible after randomisation and therefore not treated. This study is registered with ClinicalTrials.gov, NCT03088033.Findings Between May 25, 2017, and July 24, 2020, 1072 participants were enrolled, of whom 626 were randomly assigned to either the atrial shunt device (n=314) or sham procedure (n=312). There were no differences between groups in the primary composite endpoint (win ratio 1.0 [95% CI 0.8-1.2]; p=0.85) or in the individual components of the primary endpoint. The prespecified subgroups demonstrating a differential effect of atrial shunt device treatment on heart failure events were pulmonary artery systolic pressure at 20W of exercise (p(interaction)=0.002 [>70 mm Hg associated with worse outcomes]), right atrial volume index (p(interaction)=0.012 [>= 29.7 mL/m(2), worse outcomes]), and sex (p(interaction=)0.02 [men, worse outcomes]). There were no differences in the composite safety endpoint between the two groups (n=116 [38%] for shunt device vs n=97 [31%] for sham procedure; p=0.11).Interpretation Placement of an atrial shunt device did not reduce the total rate of heart failure events or improve health status in the overall population of patients with heart failure and ejection fraction of greater than or equal to 40%. Copyright (C) 2022 Elsevier Ltd. All rights reserved.

Endomyocardial biopsies are the gold standard for surveillance of graft rejection following heart transplantation, and are assessed by classical histopathology using a limited number of previously stained slices from several biopsies. Synchrotron propagation-based X-ray phase contrast imaging is a non-destructive method to image biological samples without tissue preparation, enabling virtual 2D and 3D histopathology. We aimed to show the feasibility of this method to assess acute cellular rejection and its agreement to classical histopathology. Right ventricular biopsies were sampled from 23 heart transplantation recipients (20 males, mean age 54±14 years) as part of standard follow-up. The clinical diagnosis of potential rejection was made using classical histopathology. One additional study sample was harvested and imaged by X-ray phase contrast imaging, producing 3D datasets with 0.65 μm pixel size, and up to 4,320 images per sample. An experienced pathologist graded both histopathological and X-ray phase contrast images in a blinded fashion. The agreement between methods was assessed by weighted kappa, showing substantial agreement (kappa up to 0.80, p < 0.01) between X-ray phase contrast imaging and classical histopathology. X-ray phase contrast imaging does not require tissue processing, allows thorough analysis of a full myocardial sample and allows identification of acute cellular rejection., Transplant International, 36, ISSN:0934-0874, ISSN:1432-2277

A 44-year-old female patient with chemotherapy-induced cardiomyopathy presented with acute cardiogenic shock requiring ECMO support. Multiple failed weaning trials from temporary mechanical circulatory assistance prompted a transition to staged durable biventricular support. Her course was complicated with recurrent RVAD stoppages. The initial event was treated with pump exchange, while for the subsequent RVAD standstill, we employed a device wash-out and reimplantation strategy. A brief period of circulatory arrest was employed to explore the right-sided cardiac chambers using a single-use bronchoscope.

Background Echocardiography provides complex data on cardiac function that can be integrated into patterns of dysfunction related to the severity of cardiac disease. The aim of this study was to demonstrate the feasibility of applying machine learning (ML) to automate the integration of echocardiographic data from the whole cardiac cycle and to automatically recognize patterns in velocity profiles and deformation curves, allowing the identification of functional phenotypes. Methods Echocardiography was performed in 189 clinically managed patients with hypertension and 97 healthy individuals without hypertension. Speckle-tracking analysis of the left ventricle and atrium was performed, and deformation curves were extracted. Aortic and mitral blood pool pulsed-wave Doppler and mitral annular tissue pulsed-wave Doppler velocity profiles were obtained. These whole–cardiac cycle deformation and velocity curves were used as ML input. Unsupervised ML was used to create a representation of patients with hypertension in a virtual space in which patients are positioned on the basis of the similarity of their integrated whole–cardiac cycle echocardiography data. Regression methods were used to explore patterns of echocardiographic traces within this virtual ML-derived space, while clustering was used to define phenogroups. Results The algorithm captured different patterns in tissue and blood-pool velocity and deformation profiles and integrated the findings, yielding phenotypes related to normal cardiac function and others to advanced remodeling associated with pressure overload in hypertension. The addition of individuals without hypertension into the ML-derived space confirmed the interpretation of normal and remodeled phenotypes. Conclusions ML-based pattern recognition is feasible from echocardiographic data obtained during the whole cardiac cycle. Automated algorithms can consistently capture patterns in velocity and deformation data and, on the basis of these patterns, group patients into interpretable, clinically comprehensive phenogroups that describe structural and functional remodeling. Automated pattern recognition may potentially aid interpretation of imaging data and diagnostic accuracy.

Purpose: We aimed to demonstrate the feasibility of figure of eight (FoE) suture for groin access closure in cryoballoon (CB) ablation and its impact on the lab workflow. Methods: We retrospectively analyzed all patients who underwent CB ablation in our institution from June 2018. From June 2019, we have been consistently using FoE suture for hemostasis (FoE+ group), and before that conventional manual compression was utilized (FoE- group). Ablations were performed under uninterrupted oral anticoagulant strategy. Both femoral veins were punctured, and a single introducer was placed in each vein. In the FoE- group, after ablation, protamine was administered, and manual compression was applied. In the FoE+ group, the suture was placed in both groins without protamine administration and manual compression. All patients were in decubitus position until the next morning. Results: A total of 190 consecutive patients (73.2% male, 59.7 ± 11.0 years old) were evaluated, 90 being in the FoE+ group. There was no difference in the mean procedure duration between two groups (72.7 ± 23.1 min vs 73.7 ± 27.1 min, p = 0.784). However, the total lab time was significantly longer in FoE- group (132.9 ± 35.3 min vs 109.9 ± 32.6 min, p < 0.0001). There was no difference in complication rates. No major vascular complications were found in our cohort. Conclusions: Utilization of FoE sutures for hemostasis seems to be a safe and effective after cryoballoon ablation. It abolishes the need for protamine administration which can cause serious adverse events. As manual compression is unrequired, EP lab workflow improves due to significantly shortened total lab time per patient.

Basal septal hypertrophy (BSH) is commonly seen in patients with systemic hypertension and has been associated with increased afterload. The impact of localized hypertrophy on left ventricular (LV) and left atrial (LA) function is still unclear. Our aim is to investigate if BSH is a marker of a more pronounced impact of hypertension on cardiac function in the early stages of hypertensive heart disease. An echocardiogram was performed in 163 well-controlled hypertensive patients and 22 healthy individuals. BSH was defined by a basal-to-mid septal thickness ratio ≥1.4. LV dimensions and mass were evaluated. LV global and regional deformation was assessed by 2-dimensional (2D) speckle tracking echocardiography, and LV diastolic function by 2D and Doppler imaging. LA function was evaluated with phasic volume indices calculated from 2D and 3-dimensional volumes, as well as speckle tracking echocardiography. The population was 54% men, mean age 57 (53 to 60) years. BSH was seen in 20% (n = 32) of the hypertensive cohort. Patients with BSH showed decreased regional LV systolic deformation, impaired LV relaxation with a higher proportion of indeterminate LV diastolic function, and LA functional impairment defined by a reduction of reservoir strain and a change in LA functional dynamics. In conclusion, in well-controlled hypertension impairment of LV and LA function is present in patients with early LV remodeling and localized hypertrophy. BSH might be useful as an early marker of the burden of hypertensive heart disease. This work was supported by Horizon 2020 European Commission Project H2020-MSCA-ITN- 2016 (764738), Grant from Fundacio La Marato de TV3 (040310, Exp 2015.40.30), and from Fondo de Investigaciones Sanitarias - Instituto de Salud Carlos III (PI17/ 01131).

Background: Unlike heart failure with reduced ejection fraction, there is no approved treatment for heart failure with preserved ejection fraction, the predominant phenotype in women. Therefore, there is a greater heart failure therapeutic deficit in women compared with men. Methods: In a prespecified subgroup analysis, we examined outcomes according to sex in the PARAGON-HF trial (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction), which compared sacubitril-valsartan and valsartan in patients with heart failure with preserved ejection fraction. The primary outcome was a composite of first and recurrent hospitalizations for heart failure and death from cardiovascular causes. We also report secondary efficacy and safety outcomes. Results: Overall, 2479 women (51.7%) and 2317 men (48.3%) were randomized. Women were older and had more obesity, less coronary disease, and lower estimated glomerular filtration rate and NT-proBNP (N-terminal pro–B-type natriuretic peptide) levels than men. For the primary outcome, the rate ratio for sacubitril-valsartan versus valsartan was 0.73 (95% CI, 0.59–0.90) in women and 1.03 (95% CI, 0.84–1.25) in men ( P interaction = 0.017). The benefit from sacubitril-valsartan was attributable to reduction in heart failure hospitalization. The improvement in New York Heart Association class and renal function with sacubitril-valsartan was similar in women and men, whereas the improvement in Kansas City Cardiomyopathy Questionnaire clinical summary score was less in women than in men. The difference in adverse events between sacubitril-valsartan and valsartan was similar in women and men. Conclusions: As compared with valsartan, sacubitril-valsartan seemed to reduce the risk of heart failure hospitalization more in women than in men. Whereas the possible sex-related modification of the effect of treatment has several potential explanations, the present study does not provide a definite mechanistic basis for this finding. Clinical Trial Registration: https://www.clinicaltrials.gov . Unique identifier: NCT01920711.

Aortic regurgitation (AR) following continuous flow left ventricular assist device implantation (cf-LVAD) may adversely impact outcomes. We aimed to assess the incidence and impact of progressive AR after cf-LVAD on prognosis, biomarkers, functional capacity and echocardiographic findings. In an analysis of the PCHF-VAD database encompassing 12 European heart failure centers, patients were dichotomized according to the progression of AR following LVAD implantation. Patients with de-novo AR or AR progression (AR_1) were compared to patients without worsening AR (AR_0). Among 396 patients (mean age 53 +/- 12 years, 82% male), 153 (39%) experienced progression of AR over a median of 1.4 years on LVAD support. Before LVAD implantation, AR_1 patients were less frequently diabetic, had lower body mass indices and higher baseline NT-proBNP values. Progressive AR did not adversely impact mortality (26% in both groups, HR 0.91 [95% CI 0.61-1.36]; P = 0.65). No intergroup variability was observed in NT-proBNP values and 6-minute walk test results at index hospitalization discharge and at 6-month follow-up. However, AR_1 patients were more likely to remain in NYHA class III and had worse right ventricular function at 6-month follow-up. Lack of aortic valve opening was related to de-novo or worsening AR (P < 0.001), irrespective of systolic blood pressure (P = 0.67). Patients commonly experience de-novo or worsening AR when exposed to continuous flow of contemporary LVADs. While reducing effective forward flow, worsening AR did not influence survival. However, less complete functional recovery and worse RV performance among AR_1 patients were observed. Lack of aortic valve opening was associated with progressive AR.

Cardiovascular research is in an ongoing quest for a superior imaging method to integrate gross-anatomical information with microanatomy, combined with quantifiable parameters of cardiac structure. In recent years, synchrotron radiation-based X-ray Phase Contrast Imaging (X-PCI) has been extensively used to characterize soft tissue in detail. The objective was to use X-PCI to comprehensively quantify ischemic remodeling of different myocardial structures, from cell to organ level, in a rat model of myocardial infarction. Myocardial infarction-induced remodeling was recreated in a well-established rodent model. Ex vivo rodent hearts were imaged by propagation based X-PCI using two configurations resulting in 5.8 µm and 0.65 µm effective pixel size images. The acquired datasets were used for a comprehensive assessment of macrostructural changes including the whole heart and vascular tree morphology, and quantification of left ventricular myocardial thickness, mass, volume, and organization. On the meso-scale, tissue characteristics were explored and compared with histopathological methods, while microstructural changes were quantified by segmentation of cardiomyocytes and calculation of cross-sectional areas. Propagation based X-PCI provides detailed visualization and quantification of morphological changes on whole organ, tissue, vascular as well as individual cellular level of the ex vivo heart, with a single, non-destructive 3D imaging modality., Scientific Reports, 11, ISSN:2045-2322

Background: Cardiovascular research is in an ongoing quest for a superior imaging method to integrate gross-anatomical information with microanatomy, combined with quantifiable parameters of cardiac structure. In recent years, synchrotron radiation-based X-ray Phase Contrast Imaging (X-PCI) has been extensively used to characterize soft tissue in detail.The objective was to use X-PCI to comprehensively quantify ischemic remodeling of different myocardial structures, from cell to organ level, in a rat model of myocardial infarction.Methods and Results: Myocardial infarction-induced remodeling was recreated in a well-established rodent model. Ex vivo rodent hearts were imaged by propagation based X-PCI using two configurations resulting in 5.8µm and 0.65µm effective pixel size images. The acquired datasets were used for a comprehensive assessment of macrostructural changes including the whole heart and vascular tree morphology, and quantification of left ventricular myocardial thickness, mass, volume, and organization. On the meso-scale, tissue characteristics were explored and compared with histopathological methods, while microstructural changes were quantified by segmentation of cardiomyocytes and calculation of cross-sectional areas.Conclusions: Propagation based X-PCI provides detailed visualization and quantification of morphological changes on whole organ, tissue, vascular as well as individual cellular level of the ex vivo heart, with a single, non-destructive 3D imaging modality.

BACKGROUND: There is conflicting observational data on the survival benefit cardiac implantable electronic devices (CIED) in patients with LVADs. METHODS: Patients in whom an LVAD was implanted between January 2008 and April 2017 in the multinational Trans-Atlantic Registry on VAD and Transplant (TRAViATA) registry were separated into four groups based on the presence of CIED prior to LVAD implantation: none (n = 146), implantable cardiac defibrillator (ICD) (n = 239), cardiac resynchronization without defibrillator (CRT-P) (n = 28), and CRT with defibrillator (CRT-D) (n = 111). RESULTS: A total of 524 patients (age 52 years ±12, 84.4% male) were followed for 354 (interquartile range: 166-701) days. After multivariable adjustment, there were no differences in survival across the groups. In comparison to no device, only CRT-D was associated with late right ventricular failure (RVF) (hazard ratio 2.85, 95% confidence interval [CI] 1.42-5.72, p = 0.003). There was no difference in risk of early RVF across the groups or risk of ICD shocks between those with ICD and CRT-D. CONCLUSION: In a multinational registry of patients with LVADs, there were no differences in survival with respect to CIED subtype. However, patients with a pre-existing CRT-D had a higher likelihood of late RVF suggesting significant long-term morbidity in those with devices capable of LV‑lead pacing post LVAD implantation. ispartof: INTERNATIONAL JOURNAL OF CARDIOLOGY vol:340 pages:26-33 ispartof: location:Netherlands status: published

Sacubitril-Valsartan in Acute Myocardial Infarction In a randomized trial, 5661 patients with acute myocardial infarction and a reduced left ventricular ejection fraction, pulmonary congestion, or both were assigned to receive either sacubitril-valsartan or ramipril. At a median of 22 months, there was no significant difference between the two groups in the incidence of death from cardiovascular causes or incident heart failure. Background In patients with symptomatic heart failure, sacubitril-valsartan has been found to reduce the risk of hospitalization and death from cardiovascular causes more effectively than an angiotensin-converting-enzyme inhibitor. Trials comparing the effects of these drugs in patients with acute myocardial infarction have been lacking. Methods We randomly assigned patients with myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril-valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to recommended therapy. The primary outcome was death from cardiovascular causes or incident heart failure (outpatient symptomatic heart failure or heart failure leading to hospitalization), whichever occurred first. Results A total of 5661 patients underwent randomization ; 2830 were assigned to receive sacubitril-valsartan and 2831 to receive ramipril. Over a median of 22 months, a primary-outcome event occurred in 338 patients (11.9%) in the sacubitril-valsartan group and in 373 patients (13.2%) in the ramipril group (hazard ratio, 0.90 ; 95% confidence interval [CI], 0.78 to 1.04 ; P=0.17). Death from cardiovascular causes or hospitalization for heart failure occurred in 308 patients (10.9%) in the sacubitril-valsartan group and in 335 patients (11.8%) in the ramipril group (hazard ratio, 0.91 ; 95% CI, 0.78 to 1.07) ; death from cardiovascular causes in 168 (5.9%) and 191 (6.7%), respectively (hazard ratio, 0.87 ; 95% CI, 0.71 to 1.08) ; and death from any cause in 213 (7.5%) and 242 (8.5%), respectively (hazard ratio, 0.88 ; 95% CI, 0.73 to 1.05). Treatment was discontinued because of an adverse event in 357 patients (12.6%) in the sacubitril-valsartan group and 379 patients (13.4%) in the ramipril group. Conclusions Sacubitril- valsartan was not associated with a significantly lower incidence of death from cardiovascular causes or incident heart failure than ramipril among patients with acute myocardial infarction. (Funded by Novartis ; PARADISE-MI ClinicalTrials.gov number, NCT02924727.)

BACKGROUND: Geographic variations in management and outcomes of individuals supported by continuous-flow left ventricular assist devices (CF-LVAD) between the United States (US) and Europe (EU) is largely unknown. METHODS: We created a retrospective, multinational registry of 524 patients who received a CF-LVAD (either HVAD or Heartmate II) between January 2008 and April 2017. Follow up spanned from date of CF-LVAD implant to post-HTx period with a median follow up of 44.8 months. RESULTS: The cohort included 299 (57.1%) EU and 225 (42.9%) US patients. Although the US cohort was significantly older with a higher prevalence of comorbidities, survival was similar between the cohorts (US 63.1%, EU 68.4% at 5 years, unadjusted log-rank test p = 0.43).Multivariate analyses suggested that older age, higher body mass index, elevated creatinine, use of temporary mechanical circulatory support prior CF-LVAD, and implantation of HVAD were associated with increased mortality. Among CF-LVAD patients undergoing HTx, the median time on CF-LVAD support was shorter in the US, meanwhile US donors were younger. Finally, the pattern of adverse events (stroke, gastrointestinal bleedings, late right ventricular failure, and driveline infection) during support differed significantly between US and EU. CONCLUSIONS: Although waitlisted patients in the US on CF-LVAD have higher risk comorbid conditions, the overall outcome is similar in US and EU. Geographic variations with regards to donor characteristics, duration of CF-LVAD support prior to transplant, and adverse events on support can explain the disparity in the utilization of mechanical bridge to transplant strategy between US and EU. ispartof: INTERNATIONAL JOURNAL OF CARDIOLOGY vol:324 pages:122-130 ispartof: location:Netherlands status: published

Background and aim In recent years, worse outcomes of female acute coronary syndrome (ACS) patients have been recognized. The aim was to explore gender differences in ACS in the Croatian branch of the ISACS-CT registry (NCT01218776). Methods From January 2012 to May 2018, 3066 ACS patients were enrolled; 50% (n=1539) presenting with STEMI, 35% (n=1071) with NSTEMI, and 15% (n=456) with unstable angina (UA). In-hospital mortality was defined as the primary endpoint. Results At admission women were older, more burdened with comorbidities, with a longer delay from symptom onset to admission (Figure 1), but without differences in signs and symptoms or Troponin T levels (p=0.166). During hospitalization, there were no gender difference in the administration of beta blockers, ACE inhibitors or statins in the first 24 hours. Coronary angiography was performed in a smaller percentage of female patients (86 vs. 92%, p6h (OR=1.61) were associated. At discharge, there were no gender differences in LV ejection fraction Conclusion The findings in the Croatian branch of the ISACS-CT registry demonstrate notable gender differences in ACS. Older age and a substantial burden of comorbidities represent strong influences on disease development, intervention choice and in-hospital mortality when treating women with ACS. Figure 1 Funding Acknowledgement Type of funding source: None

Artificial intelligence (AI) and machine learning (ML) in medicine are currently areas of intense exploration, showing potential to automate human tasks and even perform tasks beyond human capabilities. Literacy and understanding of AI/ML methods are becoming increasingly important to researchers and clinicians. The first objective of this review is to provide the novice reader with literacy of AI/ML methods and provide a foundation for how one might conduct an ML study. We provide a technical overview of some of the most commonly used terms, techniques, and challenges in AI/ML studies, with reference to recent studies in cardiac electrophysiology to illustrate key points. The second objective of this review is to use examples from recent literature to discuss how AI and ML are changing clinical practice and research in cardiac electrophysiology, with emphasis on disease detection and diagnosis, prediction of patient outcomes, and novel characterization of disease. The final objective is to highlight important considerations and challenges for appropriate validation, adoption, and deployment of AI technologies into clinical practice.

BACKGROUND AND AIM: The main challenge of assessing diastolic function is the balance between clinical utility, in the sense of usability and time-efficiency, and overall applicability, in the sense of precision for the patient under investigation. In this review, we aim to explore the challenges of integrating data in the assessment of diastolic function and discuss the perspectives of a more comprehensive data integration approach. METHODS: Review of traditional and novel approaches regarding data integration in the assessment of diastolic function. RESULTS: Comprehensive data integration can lead to improved understanding of disease phenotypes and better relation of these phenotypes to underlying pathophysiological processes-which may help affirm diagnostic reasoning, guide treatment options, and reduce limitations related to previously unaddressed confounders. The optimal assessment of diastolic function should ideally integrate all relevant clinical information with all available structural and functional whole cardiac cycle echocardiographic data-envisioning a personalized approach to patient care, a high-reaching future goal in medicine. CONCLUSION: Complete data integration seems to be a long-lasting goal, the way forward in diastology, and machine learning seems to be one of the tools suited for the challenge. With perpetual evidence that traditional approaches to complex problems may not the optimal solution, there is room for a steady and cautious, and inherently very exciting paradigm shift toward novel diagnostic tools and workflows to reach a more personalized, comprehensive, and integrated assessment of cardiac function. ispartof: ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES vol:37 issue:11 pages:1926-1935 ispartof: location:United States status: published

Cryoballoon (CB) is an established technology for atrial fibrillation (AF) ablation and is usually performed using solely fluoroscopy. We aimed to study the feasibility of three-dimensional rotational angiography (3DRA) as intra-procedural imaging in CB ablation. Analyzed data were retrospectively collected from patients that underwent second generation CB ablation from February 2015 to August 2017. We studied 68 consecutive patients that received 3DRA (3DRA group). Sixty-six patients who received conventional X-ray imaging served as a control group. 3DRA was performed via an introducer placed in the left atrium. Angiographic images were segmented and fused with live fluoroscopy to guide the ablation. We have analyzed 134 CB patients (73.8% male, 56.9 +/- 11.4 years). Paroxysmal AF was present in 77.6% of patients. 3DRA was successfully performed in all 3DRA group patients. The mean procedure time was significantly shorter in the control group (82.4 +/- 26.3 min) than in the 3DRA group (121.1 +/- 21.4 min) (p < 0.0001). Total radiation dose (419.3 +/- 317.9 vs 998.3 +/- 673 mGy, p < 0.0001) and contrast administration (83.2 +/- 22.3 mL vs 191.6 +/- 33.4 mL, p < 0.0001) were significantly lower in control group. There was no significant difference in 2-year success rate, 35.2% of patients had AF recurrence in the 3DRA group and 30.3% in the control group (p = 0.584). Major complications occurred in 2.9% and 1.5% of patients in 3DRA group and control group, respectively (p = 1.000). 3DRA is a feasible method of intra-procedural imaging to guide CB ablation. However, it prolongs procedure time, increases radiation dose and contrast administration with no significant effect on procedure outcomes and complication rates.

A index of non-invasive myocardial work (MWI) can account for pressure during the assessment of cardiac function, potentially separating the influence of loading conditions from the influence of the underlying tissue remodelling. The aim is to assess LV function accounted for loading and explore hypertensive MWI distribution by comparing healthy individuals to hypertensive patients without and with localized basal septal hypertrophy (BSH). An echocardiogram was performed in 170 hypertensive patients and 20 healthy individuals. BSH was defined by a basal-to-mid septal wall thickness ratio ≥ 1.4. LV speckle-tracking was performed, and the MWI calculated globally and regionally for the apical, mid and basal regions. An apex-to-base gradient, seen in regional strain values, was preserved in the distribution of myocardial work, with the apical region compensating for the impairment of the basal segments. This functional redistribution was further pronounced in patients with localized BSH. In these patients, segmental MWI analysis revealed underlying impairment of regional work unrelated to acute loading conditions. Non-invasive MWI analysis offers the possibility to compare LV function regardless of blood pressure at the time of observation. Changes in MWI distribution can be seen in hypertension unrelated to the load-dependency of strain. Accentuated functional changes affirm the role of BSH as an echocardiographic marker in hypertension.

Variability in global and regional peak strain has been thoroughly studied, but variability in spatiotemporal myocardial strain patterns has not been studied as well. This study reports on such variability and its implications for adequate disease interpretation. Forty in-training operators, distributed on 20 workstations, analyzed six cases with representative deformation patterns with commercial speckle tracking. Inter­operator differences were quantified through the variability in myocardial delineations, spatiotemporal longitudinal strain patterns and peak longitudinal strain. Intra­operator differences were assessed similarly using 10 repeated measurements from a single clinician expert. Delineations varied mainly along the lateral wall and at the valve level. Peak longitudinal strain variability was low to moderate. The spatiotemporal strain patterns were consistent despite high variability at the apex and near the valve. The results indicate that relevant pattern assessment is possible despite heterogeneous experience with speckle tracking and that careful interpretation of pattern abnormalities should be recommended before a more systematic quantitative analysis. This work was partially supported by the Spanish Ministry of Economy and Competitiveness [grant TIN2014-52923-R; Maria de Maeztu Units of Excellence Programme - MDM-2015-0502] and FEDER, and the European Union H2020 programme [PIC H2020-MSCA-ITN-2017-764738].

Background. Unlike lymphodepletion, a decrease in platelet count following induction immunosuppressive therapy with polyclonal rabbit antithymocyte globulin (rATG) is deemed as an adverse event. However, this phenomenon may represent a particular rATG antirejection mechanism. Methods. This retrospective single- center study included 156 patients who received a heart transplant (HTx) between 2010 and 2018. All patients received rATG induction therapy for 5 days. Absolute lymphocyte count (ALC) and platelet counts were assessed on days 0, 7, and 14 following HTx. The primary outcome of the study was the first occurrence of acute cellular rejection (ACR) defined as grade 1B within 24 months after HTx. Results. Both ALC and platelet counts decreased rapidly after induction. During the 24- month follow-up period, 17% of patients had ACR. Patients with ACR had significantly higher platelet count on day 7 (145 vs 104, P < 0.001) and higher ALC on day 14 (162 vs 130, P = 0.035) than those without rejection. Patients in the highest platelet count quartile showed more ACR (50% in quartile 4 vs 0% in quartile 1, P = 0.006) as well as a higher cumulative total rejection score. Univariate analysis showed that ACR was associated with platelet count on day 7, recipient age, and pretransplant cytomegalovirus IgG serology. In multivariable regression analysis, platelet count on day 7 was the most accurate predictor of ACR. Conclusions. Lower platelet count after induction with rATG is associated with less ACR. This suggests platelet involvement in antirejection mechanisms of rATG and a possible rationale for targeting platelets in future immunosuppressive strategies

Background: We aimed to analyze the rate of visualization of real-time (RT) recordings and dual fascicle electrograms in our first series of patients treated with the fourth-generation cryoballoon (CB) device. Methods: All consecutive patients who underwent CB ablation using the fourth-generation technology were included in the analysis. In all procedures, we used a 28-mm CB placed via a single transseptal puncture guided by intracardiac ultrasound. A 20- mm octapolar intraluminal circular catheter was used for intracardiac recordings. A single 180-s freeze strategy was employed. Results: A total of 129 patients (72.9% male, mean age 60.1 ± 10.9 years) were enrolled in the study. RT recordings were detected in 445 (86.2%) pulmonary veins (PVs). Specifically, RT recordings were visualized in 115 left superior PVs (89.2%), 107 left inferior PVs (82.9%), 118 right superior PVs (91.4%), and 105 right inferior PVs (81.3%). Dual fascicle electrograms could be observed only in patients in sinus rhythm, in 23 of 396 PVs (5.8%). They were most commonly observed in the left superior PV (8.1%), somewhat less in both inferior veins (6.1%), while this phenomenon was least frequent in the right superior PV (3.0%). Conclusions: By using the fourth-generation CB, we report a specific pattern of isolation represented by a sequential isolation of two apparently distinct PV fascicles during a single CB freeze delivery. This phenomenon occurred in 5.8% of PV ablations. Of note, the rate of visualization of RT isolation with this novel CB was very high and could be documented in 86.2% of PVs.

Background and aim The persistence of cardiovascular changes in fetal growth restriction (FGR) has been demonstrated from prenatal to preadolescent age, supporting the hypothesis of primary cardiac programming in FGR and the association between low birth weight and cardiovascular risk in adulthood. The aim was to follow-up the FGR cohort and explore the cardiac function and shape in adolescence. Methods FGR was defined by estimated fetal weight and birth weight below the 10th centile, while the control group consisted of normally grown fetuses with birth weight above the 10thcentile. The patients were followed from preadolescence (8–12 years of age) to adolescence (12–17 years of age) with 2-D echocardiography and deformation imaging. The adolescent participants underwent a cardiopulmonary exercise test, where echocardiography was performed at peak exercise. Sphericity index was calculated as the ratio of the LV apex-to-base length and LV basal diameter, measured in 4-chambre view. Results The cohort included 56 participants: individuals with FGR (n=22) and controls (n=34). The mean follow-up was 4.4±0.5 years. The preadolescent FGR cohort was younger (10 vs. 11 years, p=0.004), of shorter height, and lower body weight. In FGR, the trend in smaller LV end-diastolic volumes (LVEDV) was paired with a shorter apex-to-base length (63 vs. 68 mm, p=0.006), and a significantly more spherical LV (1.9 vs 2.0, p=0.004). While the LV ejection fraction was preserved, the LV global longitudinal strain (GLS) was reduced (21.21 vs 22.45%, p=0.001) and the relaxation time impaired. In the follow-up adolescent cohort, there were no differences in height, weight, LV dimensions, LV sphericity, LV GLS or relaxation time. During the follow-up period, the FGR cohort had a significantly higher increase in weight (40 vs. 31%, p=0.016) and BMI (18 vs. 11%, p=0.008). The same was seen in cardiac dimensions, showing a higher increase in LVEDV (35 vs. 27%, p=0.049) and the LV base-to-apex length (24 vs. 17%, p Conclusion The results suggest changes in cardiac shape and function, described in individuals with FGR in prenatal and preadolescent age, seem to be ameliorated in adolescence related to compensatory growth as compared to healthy controls. These findings offer novel information in the research of elevated cardiovascular risk in adults with FGR. Figure 1 Funding Acknowledgement Type of funding source: None

Objectives This study assessed the relationship between atrial fibrillation (AF) and outcomes in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, to evaluate whether AF modified the treatment response to spironolactone and whether spironolactone influenced post-randomization AF. Background AF is common in heart failure with preserved ejection fraction (HFpEF) and likely contributes to increased risk of adverse outcomes. Methods A total 1,765 patients enrolled in TOPCAT trial in North and South America were divided into 3 groups: no known AF, history of AF without AF at enrollment, and AF found on the electrocardiogram (ECG) at enrollment. We assessed outcomes and treatment response to spironolactone in all groups, and the association between post-randomization AF and outcomes in patients free of AF at baseline. The primary outcome of the TOPCAT trial was a composite of cardiovascular mortality, aborted cardiac arrest, or heart failure hospitalization. Results A total of 760 patients (43%) had a history of AF (18%) or AF on ECG at enrollment (25%). The highest adjusted risk was associated with AF at enrollment (primary outcome, hazard ratio: 1.34; 95% confidence interval: 1.09 to 1.65; p = 0.006; and an increased early risk of secondary outcomes). Neither history of AF nor AF at enrollment modified the beneficial treatment effect of spironolactone. Post-randomization AF, which occurred in 6.3% of patients, was not influenced by spironolactone treatment, but was associated with an increased early risk of the primary outcome (hazard ratio: 2.32; 95% confidence interval: 1.59 to 3.40; p Conclusions AF at enrollment was associated with increased cardiovascular risk in HFpEF patients in the TOPCAT study. Post-randomization AF, which was associated with an increased risk of morbidity and mortality, was not influenced by spironolactone. (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist [TOPCAT]; NCT00094302).

Purpose Pancyclic aortic regurgitation (AR) following continuous flow left ventricular assist device implantation (cf-LVAD) adversely impacts device performance. We present the incidence and mortality burden of progressive AR after cf-LVAD placement. Methods We conducted a retrospective analysis of a database encompassing the cf-LVAD experience of 12 European centers. Patients were dichotomized according to the progression of AR over time. Patients with de-novo AR or AR progression (group AR were compared to patients without worsening aortic valve function (group AR_0). Clinical and laboratory data were collected and compared between patient groups. Kaplan-Meier analysis was used to evaluate overall survival between cohorts. Results Out of a total of 372 eligible patients, 147 (40%) have shown progression of AR over a mean follow-up of 3.2±2.6 years. Patients in group AR_1 were comparable to group AR_0 with respect to age (57±11 vs 56±13 yrs, p=0.612), gender (81% vs 82% male, p=0.681) and preoperative INTERMACS profile (2.9±1.2 vs 2.8±1.3, p=0.715), but were found to have a lower body mass index (25±4 vs 26±5, p=0.003) and were less likely to be diabetic (14% vs 27%, P=0.003). Progressive AR did not adversely impact overall survival (Figure). The NT-pro-BNP values at index discharge were similar between groups AR_1 and AR_0 (median 2376 (IQR, 1613-4186) vs 2153 (IQR, 1357-3348), p=0.093) pg/mL and at 6-month follow-up (1632 (IQR, 1031-2567) vs 1460 (795-2331), p=0.455) pg/mL. Six-minute walk test results mirrored these data, with no observable intergroup variability at two time points (368±123 vs 386±139 meters, p=0.480 in groups AR_1 and AR_0) and (415±132 vs 487±55 meters, p=0.068). Conclusion Patients commonly experience worsening AR when exposed to the continuous flow of contemporary LVADs. While harboring potential to reduce effective forward flow by recycling the regurgitant volume, progression of AR in our study did not influence survival or functional status.