INFLA-score: A new diagnostic paradigm to identify pericarditis.

BACKGROUND: Diagnosis of pericarditis may be challenging because not all patients meet the conventional criteria. An overlooked diagnosis implies a longer course of symptoms and an increased risk of recurrences. C-reactive protein (CRP), widely used as an inflammation marker, has some limitations. This study aimed to assess the usefulness and prognostic value of INFLA-score, a validated index assessing low-grade inflammation, in the definite diagnosis of pericarditis. METHODS: Patients with suspected pericarditis were included. The INFLA-score was computed based on white blood cells and platelet count, neutrophil-to-lymphocyte ratio, and CRP, ranging from -16 to +16. An INFLA-score > 0 was considered positive for the presence of pericardial inflammation. The primary end point was the association of INFLA-score with diagnosis of pericarditis according to conventional criteria. The recurrence of pericarditis at 6 months was the secondary end point. RESULTS: A total of 202 patients were included, aged 47 ± 17 years, and 57% were females. Among 72 (36%) patients with a diagnosis of pericarditis, an INFLA-score > 0 was observed in 86% (vs. 36%, p < 0.001), abnormal CRP in 42% (vs. 10%, p < 0.001), pericardial effusion in 44% (vs. 19%, p < 0.001), abnormal electrocardiogram in 56% (vs. 24%, p < 0.001), and rubs in 5% (vs. 0.1%, p = 0.072). INFLA-score > 0 had the strongest predictive value for the diagnosis of pericarditis (hazard ratio 8.48, 95% confidence interval [CI] 3.39-21.21), with 86% sensitivity and 64% specificity, as opposed to CRP (hazard ratio 1.72, non-significant 95% CI 0.69-4.29). Recurrent pericarditis at 6 months was more frequent in patients with a positive INFLA-score (37% vs. 8%, p < 0.001, rate ratio 4.15, 95% CI 2.81-6.12). In patients with normal CRP, INFLA-score-confirmed ongoing inflammation in 78% of the cases. Compared with the conventional criteria, the INFLA-score had the highest accuracy (area under the curve = 0.82). Different cutoffs were valuable to rule out (INFLA-score > 0, sensitivity 86%, and negative likelihood ratio 0.22) or rule in (INFLA-score ≥ 10, specificity 97%, and positive likelihood ratio 13) the diagnosis. CONCLUSIONS: The INFLA-score is a useful diagnostic tool to assess the probability of pericarditis, with a strong prognostic value for further recurrences, outperforming CRP.

Efficacy of colchicine in addition to anakinra in patients with recurrent pericarditis.

AIM: Anakinra, an anti IL-1 agent targeting IL-1 alfa and beta, is available for the treatment of recurrent pericarditis in cases with corticosteroid dependence and colchicine resistance after failure of conventional therapies. However, it is unclear if the combination with colchicine, a non-specific inhibitor of the inflammasome targeting the same inflammatory pathway of IL-1, could provide additional benefit to prevent further recurrences. The aim of the present observational study is to assess whether the addition of colchicine on top of anakinra could prolong the time to first recurrence and prevent recurrences better than anakinra alone. METHODS: International, all-comers, multicentre, retrospective observational cohort study analysing all consecutive patients treated with anakinra for corticosteroid-dependent and colchicine-resistant recurrent pericarditis. The efficacy endpoint was recurrence rate and the time to the first recurrence. RESULTS: A total of 256 patients (mean age 45.0±15.4 years, 65.6% females, 80.9% with idiopathic/viral aetiology) were included. 64 (25.0%) were treated with anakinra as monotherapy while 192 (75.0%) with both anakinra and colchicine. After a follow-up of 12 months, 56 (21.9%) patients had recurrences. Patients treated with colchicine added to anakinra had a lower incidence of recurrences (respectively, 18.8% vs 31.3%; p=0.036) and a longer event-free survival (p=0.025). In multivariable analysis, colchicine use prevented recurrences (HR 0.52, 95% CI 0.29 to 0.91; p=0.021). CONCLUSIONS: The addition of colchicine on top of anakinra treatment could be helpful to reduce recurrences and prolong the recurrence-free survival.

Efficacy and safety of colchicine for the treatment of myopericarditis.

OBJECTIVE: Clinical trials have evaluated the efficacy and safety of colchicine only in simple pericarditis, excluding cases of concomitant myocarditis. The aim of this paper is to evaluate the efficacy and safety of colchicine for the treatment of the first attack of acute pericarditis with concomitant myocardial involvement. METHODS: Double-centre retrospective cohort study analysing consecutive patients admitted for first attack of pericarditis with myocarditis and treated with or without colchicine. The primary efficacy end point was the time to the first recurrence. Propensity score matching was used to generate two groups of patients with similar baseline characteristics. Colchicine-associated side effects were analysed as safety end-point. RESULTS: A total of 175 patients (mean age 46.2±20.1 years, 25.1% females, 88.6% with idiopathic/viral aetiology) were included. Seventy-nine (45.1%) patients were treated with colchicine. After a median follow-up of 25.3 (IQR 8.3-45.6) months, 58 (33.1%) patients had recurrences. The propensity score generated two groups of 73 patients with similar baseline characteristics but the use of colchicine. Patients treated with colchicine had a lower incidence of recurrences (respectively, 19.2% vs 43.8%; p=0.001) and a longer event-free survival (p=0.005). In multivariable analysis, women (HR 1.97, 95% CI 1.04 to 3.73; p=0.037) and corticosteroid use (HR 2.27, 95% CI 1.15 to 4.47; p=0.018) were independent risk factors for recurrences. Colchicine-associated side effects were mild and occurred in 3 (1.7%) patients. CONCLUSION: In patients with first attack of pericarditis associated with myocardial involvement, colchicine was safe and efficacious for the reduction of recurrences.

Transthyretin cardiac amyloidosis in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement: experience of a single center.

BACKGROUND: Even if prevalent among patients with severe aortic stenosis (AS), the clinical suspicion for transthyretin cardiac amyloidosis (ATTR-CA) remains difficult in this subset. We report our single center experience on ATTR-CA detection among TAVR candidates to provide insights on the prevalence and clinical features of dual pathology as compared to lone AS. METHODS: Consecutive severe AS patients undergoing transcatheter aortic valve replacement (TAVR) evaluation at a single center were prospectively included. Those with suspected ATTR-CA based on clinical assessment underwent 99m Tc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) bone scintigraphy. The RAISE score, a novel screening tool with high sensitivity for ATTR-CA in AS, was retrospectively calculated to rule-out ATTR-CA in the remaining patients. Patients were categorized as follow: "ATTR-CA+": patients with confirmed ATTR-CA at DPD bone scintigraphy; "ATTR-CA-": patients with negative DPD bone scintigraphy or a negative RAISE score; "ATTR-CA indeterminate": patients not undergoing ATTR-CA assessment with a positive RAISE score. The characteristics of ATTR-CA+ and ATTR-CA- patients were compared. RESULTS: Of 107 included patients, ATTR-CA suspicion was posed in 13 patients and confirmed in six. Patients were categorized as follow: 6 (5.6%) ATTR-CA+, 79 (73.8%) ATTR-CA-, 22 (20.6%) ATTR-CA indeterminate. Excluding ATTR-CA indeterminate patients, the prevalence of ATTR-CA was 7.1% (95% CI 2.6-14.7%). As compared to ATTR-CA - patients, ATTR-CA + patients were older, had higher procedural risk and more extensive myocardial and renal damage. They had higher left ventricle mass index and lower ECG voltages, translating into a lower voltage to mass ratio. Moreover, we describe for the first time bifascicular block as an ECG feature highly specific of patients with dual pathology (50.0% vs. 2.7%, P<0.001). Of note, pericardial effusion was rarely found in patients with lone AS (16.7% vs. 1.2%, P=0.027). No difference in procedural outcomes was observed between groups. CONCLUSIONS: Among severe AS patients, ATTR-CA is prevalent and presents with phenotypic features that may aid to differentiate it from lone AS. A clinical approach based on routine search of amyloidosis features might lead to selective DPD bone scintigraphy with a satisfactory positive predictive value.

Value of a short non-contrast CMR protocol in MINOCA.

OBJECTIVES: To evaluate the diagnostic performance of a short non-contrast CMR (ShtCMR) protocol relative to a matched standard comprehensive CMR (StdCMR) protocol in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA). METHODS: This multicenter retrospective study included patients with a working diagnosis of MINOCA who underwent a StdCMR between January 2019 and December 2020. An expert and a non-expert reader performed a blinded reading with the ShtCMR (long-axis cine images, T2w-STIR, T1- and T2-mapping). A consensus reading of the StdCMR (reference standard) was performed at least 3 months after the ShtCMR reading session. Readers were asked to report the following: (1) diagnosis; (2) level of confidence in their diagnosis with the ShtCMR; (3) number of myocardial segments involved, and (4) functional parameters. RESULTS: A total of 179 patients were enrolled. The ShtCMR lasted 21 ± 9 min and the StdCMR 45 ± 11 min (p < 0.0001). ShtCMR allowed reaching the same diagnosis as StdCMR in 85% of patients when interpreted by expert readers (rising from 66% for poor confidence to 99% for good, p = 0.0001) and in 73% (p = 0.01) by non-expert ones (60% for poor vs 89% for good confidence, p = 0.0001). Overall, the ShtCMR overestimated the ejection fraction, underestimated cardiac volumes (p < 0.01), and underestimated the number of segments involved by pathology (p = 0.0008) when compared with the StdCMR. CONCLUSION: The ShtCMR was found to be a debatable alternative to the StdCMR in patients with MINOCA. Nevertheless, when an experienced reader reaches a good or very good diagnostic confidence using the ShtCMR, the reader may choose to stop the examination, reducing the length of the CMR without affecting the patient's diagnosis. CLINICAL RELEVANCE STATEMENT: A short non-contrast CMR protocol may be a viable alternative to standard protocols in selected CMR studies of patients with MINOCA, allowing for faster diagnosis while reducing time and resources and increasing the number of patients who can be scanned. KEY POINTS: • The ShtCMR lasted 21 ± 9 min and the StdCMR 45 ± 11 min (p < 0.0001). • In 57% of patients with MINOCA, the experienced reader considers that contrast medium is probably not necessary for diagnosis without affecting the patient's diagnosis (99% of agreement rate between ShtCMR and StdCMR).

Cardiac imaging for the prediction of sudden cardiac arrest in patients with heart failure.

The identification of heart failure (HF) patients at risk for arrhythmic sudden cardiac arrest (SCA) is a major challenge in the cardiovascular field. In addition to optimal medical treatment for HF, implantable cardioverter defibrillator (ICD) is currently recommended to prevent SCA in patients with reduced left ventricular ejection fraction (LVEF). The indication for an ICD implantation, in addition to HF etiology, New York Health Association (NYHA) class and life expectancy, mainly depends on LVEF value at echocardiography. However, the actual role of LVEF in the prediction of SCA has recently been debated, while newer multimodality imaging techniques with increased prognostic accuracy have been developed. Speckle tracking imaging allows the quantification of mechanical dispersion, a marker of electrophysiological heterogeneity predisposing to malignant arrhythmias, while advanced cardiac magnetic resonance techniques such as myocardial T1-mapping and extracellular volume fraction assessment allow the evaluation of interstitial diffuse fibrosis. Nuclear imaging is helpful for the appraisal of sympathetic nervous system dysfunction, while newer computed tomography techniques assessing myocardial delayed enhancement allow the identification of focal myocardial scar. This review will focus on the most modern advances in the field of cardiovascular imaging along with its applications for the prediction of SCA in patients with HF. Modern artificial intelligence applications in cardiovascular imaging will also be discussed.

New Developments in the Management of Recurrent Pericarditis.

Recurrent pericarditis is a common and troublesome complication that affects 15%-30% of patients with a previous episode of pericarditis. However, the pathogenesis of these recurrences is not well understood, and most cases remain idiopathic. Recent advances in medical therapy, including the use of colchicine and anti-interleukin-1 agents like anakinra and rilonacept, have suggested an autoinflammatory rather than an autoimmune mechanism for recurrences with an inflammatory phenotype. As a result, a more personalized approach to treatment is now recommended. Patients with an inflammatory phenotype (fever and elevated C-reactive protein level) should receive colchicine and anti-interleukin-1 agents as first-line therapy, whereas those without systemic inflammation should receive low to moderate doses of corticosteroids (eg, prednisone 0.2-0.5 mg/kg/d as an initial dose) and consider azathioprine and intravenous human immunoglobulins in the case of corticosteroid failure. Tapering of corticosteroids should be slow after achieving clinical remission. In this article, we review the new developments in the management of recurrent pericarditis.

Stroke volume index and transvalvular flow rate trajectories in severe aortic stenosis treated with TAVR.

AIMS: The prognostic impact of flow trajectories according to stroke volume index (SVi) and transvalvular flow rate (FR) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) remains poorly assessed. We evaluated and compared SVi and FR prior and after TAVR for severe AS. METHODS AND RESULTS: Patients were categorized according to SVi (<35 mL/m2) and FR (<200 mL/s). The association of pre- and post-TAVR SVi and FR with all-cause mortality up to 3 years was assessed with multivariable Cox regression models. Among 980 patients with pre-TAVR flow assessment, SVi was reduced in 41.3% and FR in 48.1%. Baseline flow status was not an independent mortality predictor [SVi: hazard ratio (HR) 1.22, 95% confidence interval (CI) 0.85-1.82, FR: HR 0.78, 95% CI 0.48-1.27]. Among 731 patients undergoing early (5 days, interquartile range 2-29) post-TAVR flow assessment, SVi recovered in 40.1% and FR in 49.0% patients with baseline low flow. Reduced FR following TAVR was an independent predictor of mortality (HR 1.67, 95% CI 1.02-2.74), whereas SVi was not (HR 0.97, 95% CI 0.53-1.78). Three-year estimated mortality in patients with recovered FR was lower than that in patients with reduced FR (13.3 vs. 37.7% vs, P = 0.003) and similar to that in patients with normal baseline FR (P = 0.317). CONCLUSION: Baseline flow status was not an independent predictor of mid-term mortality among all-comers with severe AS undergoing TAVR. Flow recovery early after TAVR was frequent. Post-TAVR FR, but not SVi, was independently associated with mid-term all-cause mortality. By impacting flow status, AV replacement modifies the association of flow status with outcomes.

Colchicine for cardiovascular medicine: a systematic review and meta-analysis.

Aim: Colchicine, a microtubule-disassembling (antitubulin) agent used for centuries for the treatment of gout and autoimmune diseases, is a drug of growing interest in the cardiovascular field. While in the last decades it has become cornerstone of pericarditis treatment, it has also emerged in the last few years as a promising drug in the management of coronary artery disease, atrial fibrillation and heart failure. This systematic review and meta-analysis aimed to assess the efficacy of colchicine in patients with cardiovascular diseases. Methods: Systematic search in electronic databases (MEDLINE/PubMed, Scopus, BioMed Central, the Cochrane Collaboration Database of Randomized Trials, ClinicalTrials.gov, EMBASE, Google Scholar) was performed to identify randomized controlled trials (RCTs) up to February 2021. Random-effects meta-analysis was performed to assess the risk of cardiovascular events, defined according to clinical setting. Results: Among 15,569 pooled patients from 21 RCTs, colchicine was superior to placebo in the reduction of cardiovascular events. In the setting of pericardial diseases, it was associated with a lower risk of recurrent pericarditis (17 vs 34%, RR = 0.50, 95% CI: 0.42-0.60, I2 = 10%). In other studies assessing coronary artery disease patients, colchicine was associated with a reduced risk of major adverse cardiovascular events (MACE) such as myocardial infarction, stroke, cardiovascular death, coronary revascularisation and hospitalization (6.3 vs 9%, RR = 0.67, 95% CI: 0.54-0.84, I2 = 55). Among patients with atrial fibrillation, it was associated with lower rates of recurrence (20 vs 30%, RR = 0.68, 95% CI: 0.58-0.81, I2 = 0). In the single RCT on heart failure, colchicine was not associated with improved NYHA class. Conclusion: Colchicine is a valuable anti-inflammatory agent for the prevention of cardiovascular events in patients with inflammatory cardiac conditions such as pericardial diseases, coronary artery disease and atrial fibrillation.

Colchicine is an ancient drug with anti-inflammatory properties, classically used for gout and autoimmune diseases. While in the last decades it has become cornerstone for the treatment of pericarditis, in the last few years is emerging as a promising drug in the setting of coronary artery disease, heart failure and arrhythmias. Due to promising findings, almost ten trials are currently ongoing to investigate novel applications, which will be discussed throughout the paper. The aim of this systematic review and meta-analysis is to provide an overview of the latest evidence on colchicine, a microtubule-disassembling (antitubulin) agent, for the treatment and prevention of cardiovascular diseases and to discuss possible future applications.

An integrated approach to cardioprotection in lymphomas.

In potentially curable cancers, long-term survival depends not only on the successful treatment of the malignancy but also on the risks associated with treatment-related toxicity, especially cardiotoxicity. Malignant lymphomas affect patients at any age, with acute and late toxicity risks that could have a severe effect on morbidity, mortality, and quality of life. Although our understanding of chemotherapy-associated and radiotherapy-associated cardiovascular disease has advanced considerably, new drugs with potential cardiotoxicity have been introduced for the treatment of lymphomas. In this Review, we summarise the mechanisms of treatment-related cardiac injury, available clinical data, and protocols for optimising cardioprotection in lymphomas. We discuss ongoing research strategies to advance our knowledge of the molecular basis of drug-induced and radiation-induced toxicity. Additionally, we emphasise the potential for personalised follow-up and early detection, including the role of biomarkers and novel diagnostic tests, highlighting the role of the cardio-oncology team.

Diagnostic and prognostic role of the electrocardiogram in patients with pericarditis.

OBJECTIVE: The ECG has been traditionally used to support the diagnosis of pericarditis. However, the pericardium is electrically silent and ECG changes may imply concurrent myocardial involvement rather than simple pericarditis. The aim of the present paper is to analyse the frequency, type and clinical implication of ECG changes in patients with pericarditis compared with those with myocarditis. METHODS: Consecutive patients with pericarditis and/or myocarditis were included in a prospective cohort study from January 2017 to December 2020. A clinical and echocardiographic follow-up was performed at 1, 3, 6 months and then every 6 months. Cardiac magnetic resonance was used to diagnose concurrent myocarditis. RESULTS: 166 patients (median age 47 years, 95% CI 44 to 51) with 66 men (39.8%) were included: 110 cases with pericarditis (mean age 47.7 years, 29.1% male) and 56 cases with myocarditis (mean age 44.8, 60.7% male). ECG changes were reported in 61 of 166 (36.7%) patients: 27 of 110 (24.5%) among those with pericarditis and 34 of 56 (60.7%) among those with myocarditis (p<0.0001). In multivariate logistic regression analysis, ECG changes were associated with troponin elevation (risk ratio 1.97; 95% CI 1.13 to 3.43), suggesting myocardial involvement. ECG changes were not associated with increased risk of adverse events. CONCLUSIONS: ECG changes, mainly widespread ST-segment elevation, can be recorded in about one-quarter of patients with pericarditis, and were not associated with a worse prognosis. These changes may reflect concurrent myocarditis that should be ruled out.

Global longitudinal strain by CMR improves prognostic stratification in acute myocarditis presenting with normal LVEF.

BACKGROUND: Prognostic stratification of acute myocarditis (AM) presenting with normal left ventricular ejection fraction (LVEF) relies mostly on late gadolinium enhancement (LGE) characterization. Left ventricular peak global longitudinal strain (LV-GLS) measured by feature tracking analysis might improve prognostication of AM presenting with normal LVEF. METHODS: Data of patients undergoing cardiac magnetic resonance (CMR) for clinically suspected AM in seven European Centres (2013-2020) were retrospectively analysed. Patients with AM confirmed by CMR and LVEF ≥50% were included. LGE was visually characterized: localized versus. non-localized, subepicardial versus midwall. LV-GLS was measured by dedicated software. The primary outcome was the first occurrence of an adverse cardiovascular event (ACE) including cardiac death, life-threatening arrhythmias, development of heart failure or of LVEF <50%. RESULTS: Of 389 screened patients, 256 (66%) fulfilled inclusion criteria: median age 36 years, 71% males, median LVEF 60%, median LV-GLS -17.3%. CMR was performed at 4 days from hospitalization. At 27 months, 24 (9%) patients experienced ≥1 ACE (71% developed LVEF <50%). Compared to the others, they had lower median LV-GLS values (-13.9% vs. -17.5%, p = .001). At Kaplan-Meier analysis, impaired LV-GLS (both considered as > -20% or quartiles), non-localized and midwall LGE were associated with ACEs. Patients with LV-GLS ≤-20% did not experience ACEs. LV-GLS remained associated with ACEs after adjustment for non-localized and midwall LGE. CONCLUSION: In AM presenting with LVEF ≥50%, LV-GLS provides independent prognostic value over LGE characterization, improving risk stratification and representing a rationale for further studies of therapy in this cohort.

Unmasking the prevalence of amyloid cardiomyopathy in the real world: results from Phase 2 of the AC-TIVE study, an Italian nationwide survey.

AIM: To investigate the prevalence of amyloid cardiomyopathy (AC) and the diagnostic accuracy of echocardiographic red flags of AC among consecutive adult patients undergoing transthoracic echocardiogram for reason other than AC in 13 Italian institutions. METHODS AND RESULTS: This is an Italian prospective multicentre study, involving a clinical and instrumental work-up to assess AC prevalence among patients ≥55 years old with an echocardiogram suggestive of AC (i.e. at least one echocardiographic red flag of AC in hypertrophic, non-dilated left ventricles with preserved ejection fraction). The study was registered at ClinicalTrials.gov (NCT04738266). Overall, 381 patients with an echocardiogram suggestive of AC were identified among a cohort of 5315 screened subjects, and 217 patients completed the investigations. A final diagnosis of AC was made in 62 patients with an estimated prevalence of 29% (95% confidence interval 23%-35%). Transthyretin-related AC (ATTR-AC) was diagnosed in 51 and light chain-related AC (AL-AC) in 11 patients. Either apical sparing or a combination of ≥2 other echocardiographic red flags, excluding interatrial septum thickness, provided a diagnostic accuracy >70%. CONCLUSION: In a cohort of consecutive adults with echocardiographic findings suggestive of AC and preserved left ventricular ejection fraction, the prevalence of AC (either ATTR or AL) was 29%. Easily available echocardiographic red flags, when combined together, demonstrated good diagnostic accuracy.

Valve-in-valve transcatheter aortic valve replacement or re-surgical aortic valve replacement in degenerated bioprostheses: A systematic review and meta-analysis of short and midterm results.

INTRODUCTION: Despite limited to short and midterm outcomes, valve-in-valve (ViV) transcatheter aortic valve implantation (TAVI) has emerged as a valid alternative to re-surgical aortic valve replacement (re-SAVR) for high- and intermediate-risk patients with degenerated surgical bioprosthesis. METHODS: All studies comparing multivariate adjustment between ViV TAVI and re-SAVR were screened. The primary end-points were all-cause and cardiovascular (CV) mortality at 30 days and at Midterm follow-up. Short-term complications were the secondary endpoints. RESULTS: We obtained data from 11 studies, encompassing 8570 patients, 4224 undergoing ViV TAVI, and 4346 re-SAVR. Four studies included intermediate-risk patients and seven high-risk patients. 30-day all-cause and CV mortality were significantly lower in ViV (odds ratio [OR] 0.43, 95% confidence intervals [CIs] 0.29-0.64 and OR 0.44, 0.26-0.73 respectively), while after a mean follow-up of 717 (180-1825) days, there was no difference between the two groups (OR 1.04, 0.87-1.25 and OR 1.05, 0.78-1.43, respectively). The risk of stroke (OR 1.03, 0.59-1.82), MI (OR 0.70, 0.34-1.44), major vascular complications (OR 0.92, 0.50-1.67), and permanent pacemaker implantation (OR 0.67, 0.36-1.25) at 30 days did not differ, while major bleedings and new-onset atrial fibrillation were significantly lower in ViV patients (OR 0.41, 0.25-0.67 and OR 0.23, 0.12-0.42, respectively, all 95% CIs). CONCLUSIONS: In high- and intermediate-risk patients with degenerated surgical bioprostheses, ViV TAVI is associated with reduced short-term mortality, compared with re-SAVR. Nevertheless, no differences were found in all-cause and CV mortality at midterm follow-up. PROSPERO CRD42021226488.

Incidence trends and long-term outcomes of myocardial infarction in young adults: Does gender matter?

AIMS: Data about long-term clinical outcomes of young patients experiencing an acute myocardial infarction (MI) and about the potential impact of gender on juvenile MI incidence and prognosis are scant. METHODS AND RESULTS: Hospital Discharge Register records of Piedmont region (Italy) from 2007 to 2018 were interrogated to identify incident juvenile MI cases and MI recurrences. Patients were considered young if the first MI occurred before or at 47 years of age (5th percentile). Incidence of first juvenile MI event and overall survival were the primary outcomes. Gender differences and survival rate after an MI recurrence were secondary outcomes. Out of 114.816 hospitalizations due to MI, 4482 (3.9%) occurred in people aged ≤47. Average incidence rate of juvenile MI over the study period was 24.5 (23.8-25.2) per 100.000 person-years, with a decline among men and a stable trend among women through the years. The risk of in hospital death was higher for women (1.9% vs. 0.9%, p = 0.02), while the survival rate at 10 years after the first MI was 94.8%, without gender differences (HR 1.05: 0.69-1.60). MI recurrence occurred in 348 (7.8%) and was less common in women (HR 0.72: 0.52-0.99). After multivariate adjustment, MI recurrence was associated with a significantly higher risk of death at follow-up as compared with a single MI episode (HR 3.05: 1.9-4.80, all CI 95%). CONCLUSION: Among young patients with MI, women had a higher in-hospital mortality compared to men, but long-term prognosis after hospital discharge did not differ. MI recurrences were associated with increased mortality at follow up.

Prognostic implications of impaired longitudinal left ventricular systolic function assessed by tissue Doppler imaging prior to transcatheter aortic valve implantation for severe aortic stenosis.

Change in longitudinal left ventricular (LV) systolic function serves as an early marker of the deleterious effect of aortic stenosis (AS) and other cardiac comorbidities on cardiac function. We explored the prognostic value of tissue Doppler imaging (TDI)-derived longitudinal LV systolic function, defined by the peak systolic average of lateral and septal mitral annular velocities (average S') among symptomatic patients with severe AS undergoing transcatheter aortic valve implantation (TAVI). 297 consecutive patients with severe AS undergoing TAVI at three european centers with available average S' at preprocedural echocardiography were retrospectively included. The primary endpoint was the Kaplan Meier estimate of all-cause mortality. After a median 18 months (IQR 12-18) follow-up, 36 (12.1%) patients had died. Average S' was associated with all-cause mortality (per 1 cm/sec decrease: HR 1.29, 95%CI 1.03-1.60, p = 0.025), the cut-off of 6.5 cm/sec being the most accurate. Patients with average S' < 6.5 cm/sec (55.2%) presented characteristics of more advanced LV remodeling and functional impairment along with higher burden of cardiac comorbidities, and experienced higher all-cause mortality (17.6% vs. 7.5%, p = 0.007), also when adjusted for in-study outcome predictors (adj-HR: 2.69, 95%CI 1.22-5.93, p = 0.014). Results were consistent among patients with preserved ejection fraction, normal-flow AS, high-gradient AS and in those without LV hypertrophy. Longitudinal LV systolic function assessed by average S' is independently associated with long-term all-cause mortality among TAVI patients. An average S' below 6.5 cm/sec best defines clinically meaningful reduced longitudinal systolic function and may aid clinical risk stratification in these patients.

Efficacy and safety of colchicine for the prevention of major cardiovascular and cerebrovascular events in patients with coronary artery disease: a systematic review and meta-analysis on 12 869 patients.

AIMS: The key role of inflammation in the pathogenesis of coronary artery disease (CAD) is an urgent call for innovative treatments. Several trials have proposed colchicine as a therapeutic option for secondary prevention in CAD patients but its utilization is hampered by fears about drug-related adverse events (DAEs) and conflicting evidences. The aim of this meta-analysis was to consolidate evidence on the efficacy and safety of colchicine for secondary prevention in patients with CAD. METHODS AND RESULTS: A systematic search in electronic bibliographic databases of Medline, Scopus, Embase, and the Cochrane Library was performed to identify randomized controlled trials (RCTs) assessing the cardiovascular effects of colchicine in CAD patients, compared with placebo. Outcomes of interest were the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) and DAEs. Estimates were pooled using inverse-variance random-effects model. A total of 11 RCTs, including 12 869 patients, were identified as eligible. A total of 6501 patients received colchicine, while 6368 received placebo. After a median follow-up of 6 months (interquartile range, 1-16), patients receiving colchicine had a lower risk of MACCE [6% vs. 8.8%, relative risk (RR) = 0.67, 95% confidence interval (CI) 0.56-0.80, I2 = 19%], myocardial infarction (3.3% vs. 4.3%, RR = 0.76, 95% CI 0.61-0.96, I2 = 17%), coronary revascularization (2.9% vs. 4.2%, RR = 0.61, 95% CI 0.42-0.89, I2 = 40%), stroke (0.4% vs. 0.9%, RR = 0.48, 95% CI 0.30-0.77, I2 = 0%), hospitalization for cardiovascular cause (0.9% vs. 2.9%, RR = 0.32, 95% CI 0.12-0.87, I2 = 0%). Colchicine was associated with an increased risk of gastrointestinal DAEs (11% vs. 9.2%, RR = 1.67, 95% CI 1.20-2.34, I2 = 76%), myalgia (18% vs. 16%, RR = 1.16, 95% CI 1.02-1.32, I2 = 0%) and DAEs-related discontinuation (4.1% vs. 3%, RR = 1.54, 95% CI 1.02-2.32, I2 = 65%). However, gastrointestinal DAEs and discontinuation may be prevented with a lower daily dose. Colchicine did not increase the risk of cardiovascular death (0.7% vs. 1%, RR = 0.73, 95% CI 0.45-1.21, I2 = 14%), all-cause death (2% vs. 1.9%, RR = 1.01, 95% CI 0.71-1.43, I2 = 16%), or other DAEs. CONCLUSIONS: The use of colchicine in patients with CAD is safe and efficacious for MACCE prevention.

Prognostic role of left atrial enlargement in patients with implantable cardioverter defibrillators for primary prevention.

PURPOSE: Left atrial volume index (LAVI) is a predictor of heart failure and adverse events, irrespective of left ventricular systolic function. The role of LAVI in the prediction of appropriate implantable cardioverter-defibrillator (ICD) therapies is currently unclear and was the focus of this study. METHODS: Consecutive heart failure patients with ischaemic (ICM) or idiopathic (DCM) aetiology receiving ICD for primary prevention were included. The primary endpoint was the occurrence of appropriate ICD therapies (ATs): shocks or antitachycardia pacing (ATP). Inappropriate ICD shocks were also assessed as secondary endpoint. RESULTS: Among 198 included patients, severe left atrial dilatation (SLAE = LAVI ≥ 60 ml/m2) was present in 54 (27%). SLAE patients had a higher prevalence of NYHA class ≥ III, severe mitral regurgitation and atrial fibrillation history. During a median follow-up of 45 months (IQR 25-68), ATs occurred more frequently in SLAE group (33% vs. 15%, p = .007) as well as appropriate shocks (24% vs. 10%, p = .014). At multivariate analysis SLAE was an independent predictor of ATs (OR 3.19, 95% CI 1.38-7.38, p = .007). Inappropriate shocks were associated with AF during implantation (p = .03), but not with SLAE (p = .009). CONCLUSION: In DCM or ICM patients candidate to receive an ICD for primary prevention, a severely enlarged left atrium is a predictive factor for ATs (shocks or ATP). The risk of inappropriate shocks was increased in patients with atrial fibrillation, rather than SLAE.

Impact of computed-tomography defined sarcopenia on outcomes of older adults undergoing transcatheter aortic valve implantation.

BACKGROUND: The adoption of Computed tomography (CT)-defined sarcopenia to risk stratify transcatheter aortic valve implantation (TAVI) candidates remains limited by a lack of both standardized definition and evidence of independent value over currently adopted mortality prediction tools. METHODS: 391 consecutive TAVI patients with pre-procedural CT scan were included (81 â€‹± â€‹6 years, 57.5% male, STS-PROM score 4.4 â€‹± â€‹3.6%) and abdominal muscle retrospectively quantified. The two definitions of radiologic sarcopenia previously adopted in TAVI studies were compared (psoas muscle area [PMA] at the L4 vertebra level: "PMA-sarcopenia"; indexed skeletal muscle area at the L3 vertebra level: "SMI-sarcopenia"). The primary endpoint was longer available-term all-cause mortality. Secondary endpoints were Valve Academic Research Consortium-2-defined in-hospital and 30-day outcomes. RESULTS: SMI- and PMA-sarcopenia were present in 192 (49.1%) and 117 (29.9%) patients, respectively. After a median of 24 (12-30) months follow-up, 83 (21.2%) patients died. PMA-(adj-HR 1.81, 95%CI 1.12-2.93, p â€‹= â€‹0.015), but not SMI-sarcopenia (adj-HR 1.23, 95%CI 0.76-2.00, p â€‹= â€‹0.391), was associated with all-cause mortality independently of age, sex and in-study outcome predictors (atrial fibrillation, hemoglobin, history of peripheral artery disease, cancer and subcutaneous adipose tissue). PMA-defined sarcopenia provided additive prognostic value over current post-TAVI mortality risk estimators including STS-PROM (p â€‹= â€‹0.001), Euroscore II (p â€‹= â€‹0.025), Charlson index (p â€‹= â€‹0.025) and TAVI2-score (p â€‹= â€‹0.020). Device success, early safety, clinical efficacy and 30-day all-cause death were unaffected by sarcopenia status regardless of definition. CONCLUSIONS: PMA-sarcopenia (but not SMI-sarcopenia) is predictive of 2 year mortality among TAVI patients. The prognostic information provided by PMA-sarcopenia is independent of the tools currently adopted to predict post-TAVI mortality in clinical practice.