Abstract Background Arrhythmic mitral valve prolapse (AMVP) is characterized by an arrhythmogenic left ventricular substrate, with high prevalence of myocardial scar. Whether patients with prior mitral valve repair for mitral valve prolapse (MVP) and new-onset complex ventricular arrhythmias (VAs) after cardiac surgery have different electroanatomical substrate and arrhythmic outcomes compared with AMVP patients without prior mitral valve surgery is currently unknown. Purpose We sought to compare the electroanatomical substrate and long-term clinical outcomes of patients with new-onset complex VAs after mitral valve surgery to AMVP patients without prior surgery. Methods We conducted a multicenter, prospective, observational study, enrolling MVP patients with prior mitral valve repair and new-onset complex VAs (>1000 premature ventricular contractions [PVCs]/day, nonsustained ventricular tachycardia [NSVT], and sustained VT) after cardiac surgery (group A,n=9), and patients with MVP, complex VAs and no prior surgery (group B,n=20). Each patient underwent a comprehensive diagnostic workup, including left ventricular electroanatomical mapping. Clinical-imaging data, as well as the location and segmental extension of both low-voltage areas and late potentials were assessed and compared between the two groups. The primary outcome was the occurrence of sustained VT or ventricular fibrillation(VF) during follow-up. Results In group A, complex VAs were first diagnosed after a median of 30(8-56) months following mitral valve repair. The characteristics of patients from the two study groups are presented in the Table. Patients from group A were older, sustained VT was nonsignificantly more common at baseline, the PVC count nonsignificantly higher, and LVEF nonsignificantly lower. Mitral annular disjunction was never observed in group A, while it was found in 7 patients from group B (p=0.066). At LV electroanatomical voltage mapping, bipolar and unipolar low-voltage areas (LVAs) were equally common in the two groups overall, and typically involved basal perimitral regions. However, patients from group B had concomitant bipolar and unipolar LVAs 50% of times, with larger unipolar LVAs, while patients from group A mostly showed isolated bipolar LVAs. Over a median follow-up of 15 (12-41) months, patients from group A (n=3, 33%) had slightly higher incidence of sustained VT or VF (HR: 1.91; 95% CI, 1.06-42.65; log-rank p=0.02, Figure) than patients from group B (n=2, 10%). Conclusion Compared to patients with AMVP and no prior cardiac surgery, patients with new-onset complex VAs after mitral valve repair for MVP have a slightly different clinical profile and electroanatomical substrate, characterized by predominant bipolar LVAs in the perimitral region. The long-term risk of major ventricular arrhythmias appears slightly higher in MVP patients with prior mitral valve surgery, mandating at least an equally careful risk assessment in both groups.

Abstract Background Pulmonary arterial hypertension (PAH) is a rare, progressive disease leading to right-sided heart failure. The interest in risk assessment based on non-invasive parameters is growing, and insights from clinical practice are needed in this regard. INSPECTIO is an Italian observational study aimed at filling this knowledge gap. The results of an interim analysis at month 12 are presented below. Purpose The primary objective was to assess the change from baseline to month 12 in the number of the non-invasive low-risk parameters among World Health Organization functional class, 6-minutes walking distance, Brain Natriuretic Peptide (BNP) or N-terminal proBNP. Secondary objectives are the evaluation of echocardiographic and haemodynamic parameters, and the proportion of patients in which the therapy was optimized according to the guidelines. Methods Prospective, multicentre study on PAH patients at low/intermediate mortality risk treated with macitentan and/or selexipag as part of the oral combination therapy. Results Among 177 patients who were enrolled in 29 centres, 148 patients [median age 63.0 years (Q1/Q3: 53.5/73.0), 76.4% females] completed the 12-month follow up and were considered for this analysis. The median time from PAH diagnosis was 22.6 months (4.9/60.1). Sixty-four (43.2%) patients had idiopathic PAH; 4 (2.7%) heritable; 80 (54.1%) associated with other diseases [58 (72.5%) connective tissue disease, 11 (13.8%) congenital heart disease corrected for at least one year, 5 (6.3%) portal hypertension, 5 (6.3%) human immunodeficiency virus infection, 1 (1.3%) drug and toxins]. At baseline, 45.9% patients and 28.4% were in double and triple oral combination therapy, respectively. Primary objective: at month 12, the number of noninvasive low-risk parameters increased in 43 (29.1%) patients and remained stable in 80 (54.1%) patients [mean change 0.16 (p=0.017)]. The values at baseline, at month 12 and the change from baseline for each noninvasive parameter are shown in Table 1. Mean right atrial (RA) area (end-systole) and tricuspid annular plane systolic excursion (TAPSE) remained unchanged while a reduction of systolic pulmonary artery pressure (sPAP) was observed. Regarding the haemodynamic parameters, the mean pulmonary arterial pressure decreased [median change -4.5, (p=0.0346)], while cardiac index, pulmonary vascular resistance, and RA pressure remained stable (Table 2). The number of patients on triple therapy increased from 42 to 51 (+21.4%). Conclusions This study confirms that a noninvasive low-risk profile can be achieved with current combination PAH therapy. The modest or absent changes in echocardiographic and hemodynamic parameters suggest that treatment of PAH in real world is yet to be improved; on the other hand, the optimization of therapy in a significant portion of patients can possibly account for the improvement or stabilization observed.Noninvasive parametersEcho and hemodynamic parameters

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiac amyloidoses (CA) are an increasingly recognized group of infiltrative cardiomyopathies associated with high risk of heart failure, thromboembolic events, arrhythmias, and sudden death. Endomyocardial biopsy may be required to differentiate the amyloid type (mainly, Immunoglobulin light chain [AL] versus transthyretin-related [ATTR]) in some cases. Purpose to provide a first description of electroanatomical characteristics of amyloid cardiomyopathy, and relate them to endomyocardial biopsy findings. Methods we enrolled ten consecutive patients (median age, 68 [63-77]; male, 50%) in an observational, retrospective study. All of them had a clinical diagnosis of CA, but a diagnosis of CA type was hampered by the presence of inconclusive or discordant laboratory-imaging findings (abnormal serum free light chain assay and positive bone scintigraphy, n=5; ambiguous imaging results, n=4; abnormal serum free light chain assay and TTR gene mutation, n=1). Therefore, all patients underwent right ventricular high-density electroanatomical mapping (EAM) using a multipolar catheter (Advisor HD Grid, Abbott), and EAM-guided endomyocardial biopsy (EMB). We recorded electrogram features at EMB sampling site, and explored their correlation with histological findings with mixed effect models. Results The clinical, electroanatomical, and histological features of enrolled patients according to the EMB-proven type of CA (AL, n=6; ATTR, n=4) are resumed in Table. Electrogram amplitudes in both the bipolar and the unipolar configuration were generally normal both in the overall right ventricle, and at EMB sites. We found a significant correlation between both unipolar and bipolar electrogram amplitude and the percentage of both amyloid tissue (p<0.01 and p=0.016, respectively) and fibrous tissue (both p<0.01) at EMB (Figure). We observed the strongest linear association (i.e., highest R2) between unipolar electrogram amplitude and amyloid tissue, as well as between bipolar electrogram amplitude and fibrous tissue. On the other hand, electrogram duration and the number of electrogram peaks were unrelated to histological findings. The unipolar voltage cutoff that best identified regions with >15% amyloid tissue infiltration according to Youden index was 9.1 mV (sensitivity, 43%; specificity, 100%; accuracy, 77%). Conclusion CA is associated with normal electrogram amplitudes using ahigh density mapping catheter and conventional voltage cutoffs. Nevertheless, unipolar electrogram amplitude is strongly related to the extent of amyloid infiltration, and unipolar voltage<9.1 mV is 100% specific for >15% amyloid tissue deposition. Clinical-instrumental characteristics EAM-EMB correlations

Abstract Background Cardiac amyloidoses (CA) are an increasingly recognized group of infiltrative cardiomyopathies associated with high risk of major adverse cardiac events. Endomyocardial biopsy (EMB) may be required to differentiate the amyloid type (mainly, Immunoglobulin light chain [AL] versus transthyretin-related [ATTR]) in some cases. Purpose The aim of this study was to provide the first description of the right ventricular (RV) electroanatomical substrate of CA, and assess its association with EMB findings and clinical outcomes. Methods We enrolled ten consecutive patients undergoing EMB for suspected CA (median age, 68[63-77]; male, 50%) in a monocentric, observational, retrospective study. All patients had a clinical diagnosis of CA, but a diagnosis of CA type was hampered by the presence of inconclusive or discordant laboratory-imaging findings (abnormal serum free light chain assay and positive bone scintigraphy, n=5; ambiguous imaging results, n=4; abnormal serum free light chain assay and TTR gene mutation, n=1). Therefore, each patient underwent RV high-density electroanatomical voltage mapping (EVM) and EMB. The primary outcome was death or hospitalization at 1-year follow-up. We recorded electrogram features at EMB sampling sites and in the overall RV, and explored their correlations with histopathological findings and primary outcomes events. Results A final EMB-proven diagnosis of AL or ATTR CA was formulated in 6 and 4 patients, respectively. Electrogram amplitudes in the bipolar and unipolar configurations averaged 1.58±0.65 mV, and 5.38±1.41 in the overall RV. We found a significant inverse correlation between unipolar electrogram amplitude and amyloid burden at EMB (p<0.001); the unipolar voltage cutoff that best identified regions with >15% amyloid tissue infiltration according to Youden index was 9.1 mV (sensitivity, 43%; specificity, 100%; accuracy, 77%). At 1-year follow-up, 6 patients (60%) experienced a primary outcome event. Compared to subjects with uneventful follow-up, patients with a primary outcome event had larger unipolar low-voltage zones (32.3 [6.1] cm2 vs. 20.7 [6.5] cm2, p=0.043) and bipolar dense scar areas (6.1 [2.3] cm2 vs. 1.8 [0.7] cm2, p=0.005), and after pooling mapping points from all patients, unipolar electrogram amplitude was moderately associated with primary outcome events (AUC: 0.65 [95% CI, 0.64-0.65]). Conclusions In CA, electrogram amplitudes are around the lower limit of normal, yet disproportionately low compared to the increased wall thickness. We found evidence that unipolar electrogram amplitude may be a quantitative marker of amyloid burden, possibly associated with adverse clinical outcomes.EVM and EMB in ATTR cardiac amyloidosisEVM and EMB in AL cardiac amyloidosis

Background: pulmonary arterial hypertension (PAH) is a chronic, progressive disease; the use of narrative medicine may help investigate patient perspective, their self-perception and quality of life to better address the burden of disease. Aims: to gain insights into how PAH patient and their caregivers experience PAH, by evaluating narrative plots collected within the INSPECTIO study. Methods: INSPECTIO is an ongoing, observational, multicentre, prospective study of patients with PAH. We aimed to enrol 200 already diagnosed patients and already in treatment with macitentan and/or selexipag as part of combination therapy. Enrolment began in November 2020 and narratives are collected from patients and their caregivers at enrolment of the patients (V1) and at 12 months, then analysed through MAXQDA software. Results: as of January 2022, the study has enrolled 96 patients; 62 of them and 12 caregivers accepted to write narrative plots of their experience, and 17 patients (13 women, mean age 59 years) and 6 caregivers (4 spouses) completed V1 narrative plots. The narratives highlight the anguish and concern experienced by caregivers. For patients, despite confusion at diagnosis, they reported an improvement in their general condition over time. Nonetheless, only few patients describe PAH as a battle to be fought, while “threat” and “limitation” are the words mainly used to describe the disease. Conclusion: to our knowledge, this is the first PAH study using narrative medicine. Preliminary findings suggest that caregivers might feel a heavier burden of PAH than patients themselves and this should be considered in clinical practice to help managing this illness.

Aims The analysis evaluated the contemporary percentage of patients with established coronary heart disease (CHD) reaching the European guidelines recommended LDL-cholesterol (LDL-C) levels of less than 70 mg/dl and the threshold required for proprotein convertase subtlisin/kexin type 9 reimbursement in Italy (100 mg/dl). It also assessed how these percentages would change in case of diffuse use of ezetimibe. Methods The Dyslipidemia International Study II enrolled CHD patients aged at least 18 either on lipid-lowering therapy (LLT) for at least 3 months or not on LLT at the time of the lipid profile. Distribution of LLTs and LDL-C target attainment were assessed. Multivariate logistic regression evaluated predictors of LDL-C target attainment. A 24% LDLC lowering was modeled in patients not taking ezetimibe to assess its potential effects. Results Among 676 Italian CHD patients enrolled, LDL-C concentrations were lower among the 631 patients (93.3%) who were on LLT (82 versus 118 mg/dl; P< 0.001). The LDLC target was attained by 35.4% of patients. Statin dose (median atorvastatin dose 40 mg/day) was the sole significant predictor of LDL-C target attainment The simple addition of ezetimibe in the model reduced the percentage of patients more than 70 and 100 mg/dl from 64.6 to 37.9% and from 25.1 to 11.8%, respectively. Conclusion Despite treatment in more than 90%, only one-third of Italian stable CHD patients attained the recommended LDL-C target Statin dose was the sole predictor of the target achievement The addition of ezetimibe would almost double patients at target and halve the potential candidates for reimbursement of more expensive agents such as proprotein convertase subtlisin/kexin type 9 inhibitors.

Background The Universal Definition of Myocardial Infarction recommends the 99th percentile concentration of cardiac troponin in a normal reference population as part of the decision threshold to diagnose type 1 spontaneous myocardial infarction. Adoption of this recommendation in contemporary worldwide practice is not well known.Methods We performed a cohort study of 276 hospital laboratories in 31 countries participating in the National Heart, Lung, and Blood Institute sponsored International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial. Each hospital laboratory's troponin assay manufacturer and model, the recommended assay's 99th percentile upper reference limit (URL) from the manufacturer's package insert, and the troponin concentration used locally as the decision level to diagnose myocardial infarction were ascertained.Results Twenty-one unique troponin assays from 9 manufacturers were used by the surveyed hospital laboratories. The ratio of the troponin concentration used locally to diagnose myocardial infarction to the assay manufacturer determined 99th percentile URL was < 1 at 19 (6.6%) laboratories, equal to 1 at 91 (31.6%) laboratories, > 1 to < 5 at 101 (35.1%) laboratories, > 5 to <= 10 at 34 (11.8%) laboratories, and > 10 at 43 (14.9%) laboratories. The variability in troponin decision level for myocardial infarction relative to the assay 99th percentile URL was present for laboratories in and outside of the United States, as well as for high- and standard-sensitivity assays.Conclusions There is substantial hospital-level variation in the troponin threshold used to diagnose myocardial infarction; only one-third of hospital laboratories currently follow the Universal Definition of Myocardial Infarction consensus recommendation for use of troponin concentration at the 99th percentile of a normal reference population as the decision level to diagnose myocardial infarction. This variability across laboratories has important implications for both the diagnosis of myocardial infarction in clinical practice as well as adjudication of myocardial infarction in clinical trials.

AIMSPatients with acute coronary syndromes (ACSs) who are managed without coronary revascularization represent a mixed and understudied population that seems to receive suboptimal pharmacological treatment.METHODS AND RESULTSWe assessed patterns of antithrombotic therapies employed during the hospitalization and in-hospital clinical events of medically managed patients with ACS enrolled in the prospective, multicentre, nationwide EYESHOT (EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalized in iTalian cardiac care units) registry. Among the 2585 consecutive ACS patients enrolled in EYESHOT, 783 (30.3%) did not receive any revascularization during hospital admission. Of these, 478 (61.0%) underwent coronary angiography (CA), whereas 305 (39.0%) did not. The median GRACE and CRUSADE risk scores were significantly higher among patients who did not undergo CA compared with those who did (180 vs. 145, P < 0.0001 and 50 vs. 33, P < 0.0001, respectively). Antithrombotic therapies employed during hospitalization significantly differ between patients who received CA and those who did not with unfractioned heparin and novel P2Y12 inhibitors more frequently used in the first group, and low-molecular-weight heparins and clopidogrel in the latter group. During the index hospitalization, patients who did not receive CA presented a higher incidence of ischaemic cerebrovascular events and of mortality compared with those who underwent CA (1.6 vs. 0.2%, P = 0.04 and 7.9 vs. 2.7%, P = 0.0009, respectively).CONCLUSIONAlmost one-third of ACS patients are managed without revascularization during the index hospitalization. In this population, a lower use of recommended antiplatelet therapy and worse clinical outcome were observed in those who did not undergo CA when compared with those who did.CLINICAL TRIAL REGISTRATIONUnique identifier: NCT02015624, http://www.clinicaltrials.gov.

Stress echocardiography (SE) is dependent on subjective interpretations. As a prelude to the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) Trial, potential sites were required to submit two SE, one with moderate or severe left ventricular (LV) myocardial ischemia and one with mild ischemia. We evaluated the concordance of site and core lab interpretations.