Echocardiographic and clinical features of patients developing prosthesis-patient mismatch after TAVR: insights from the Recovery TAVR registry.

BACKGROUND: The impact of prosthesis-patient mismatch (PPM) on major endpoints after transcatheter aortic valve replacement (TAVR) is controversial and the effects on progression of heart damage are poorly investigated. Therefore, our study aims to evaluate the prevalence and predictors of PPM in a "real world" cohort of patients at intermediate and low surgical risk, its impact on mortality and the clinical-echocardiographic progression of heart damage. METHODS: 963 patients who underwent TAVR procedure between 2017 and 2021, from the RECOVERY-TAVR international multicenter observational registry, were included in this analysis. Multiparametric echocardiographic data of these patients were analyzed at 1-year follow-up (FU). Clinical and echocardiographic features were stratified by presence of PPM and PPM severity, as per the most current international recommendations, using VARC-3 criteria. RESULTS: 18% of patients developed post-TAVR. PPM, and 7.7% of the whole cohort had severe PPM. At baseline, 50.3% of patients with PPM were male (vs 46.2% in the cohort without PPM, p=0.33), aged 82 (IQR 79-85y) years vs 82 (IQR 78-86 p=0.46), and 55.6% had Balloon-Expandable valves implanted (vs 46.8% of patients without PPM, p=0.04); they had smaller left ventricular outflow tract (LVOT) diameter (20 mm, IQR 19-21 vs 20 mm, IQR 20-22, p=0.02), reduced SVi (34.2 vs 38 ml/m2, p<0.01) and transaortic flow rate (190.6 vs 211 ml/s, p<0.01). At pre-discharge FU patients with PPM had more paravalvular aortic regurgitation (moderate-severe AR 15.8% vs 9.2%, p<0.01). At 1-year FU, maladaptive alterations of left ventricular parameters were found in patients with PPM, with a significant increase in end-systolic diameter (33 mm vs 28 mm, p=0.03) and a significant increase in left ventricle end systolic indexed volume in those with moderate and severe PPM (52 IQR 42-64 and 52, IQR 41-64 vs.44 IQR 35-59 in those without, p=0.02)). No evidence of a significant impact of PPM on overall (p=0.71) and CV (p=0.70) mortality was observed. Patients with moderate/severe PPM had worse NYHA functional class at 1 year (NYHA III-IV 13% vs 7.8%, p=0.03). Prosthesis size≤23 mm (OR 11.6, 1.68-80.1) was an independent predictor of PPM, while SVi (OR 0.87, 0.83-0.91, p<0.001) and LVOT diameter (OR 0.79, 0.65-0.95, p=0.01) had protective effect. CONCLUSIONS: PPM was observed in 18% of patients undergoing TAVR. Echocardiographic evaluations demonstrated a PPM-related pattern of early ventricular maladaptive alterations, possibly precursor to a reduction in cardiac function, associated with a significant deterioration in NYHA class at 1 year. These findings emphasize the importance of prevention of PPM of any grade in patients undergoing TAVR procedure, especially in populations at risk.

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).

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.

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.

Usefulness of oral anticoagulation in patients with coronary aneurysms: Insights from the CAAR registry.

OBJECTIVES: To assess the Usefulness of oral anticoagulation therapy (OAT) in patients with coronary artery aneurysm (CAA). BACKGROUND: Data on the most adequate antithrombotic CAA management is lacking. METHODS: Patients included in CAAR (Coronary Artery Aneurysm Registry, Clinical Trials.gov: NCT02563626) were selected. Patients were divided in OAT and non-OAT groups, according to anticoagulation status at discharge and 2:1 propensity score matching with replacement was performed. The primary endpoint of the analysis was a composite and mutual exclusive endpoint of myocardial infarction, unstable angina (UA), and aneurysm thrombosis (coronary ischemic endpoint). Net adverse clinical events, major adverse cardiovascular events, their single components, cardiovascular death, re-hospitalizations for heart failure, stroke, aneurysm thrombosis, and bleeding were the secondary ones. RESULTS: One thousand three hundred thirty-one patients were discharged without OAT and 211 with OAT. In the propensity-matched sample (390 patients in the non-OAT group, 195 patients in the OAT group), after 3 years of median follow-up (interquartile range 1-6 years), the rate of the primary endpoint (coronary ischemic endpoint) was significantly less in the OAT group as compared to non-OAT group (8.7 vs. 17.2%, respectively; p = .01), driven by a significant reduction in UA (4.6 vs. 10%, p < .01) and aneurysm thrombosis (0 vs. 3.1%, p = .03), along with a non-significant reduction in MI (4.1 vs. 7.7%, p = .13). A non-significant increase in bleedings, mainly BARC type 1 (55%), was found in the OAT-group (10.3% in the non-OAT vs. 6.2% in the OAT group, p = .08). CONCLUSION: OAT decreases the composite endpoint of UA, myocardial infarction, and aneurysm thrombosis in patients with CAA, despite a non-significant higher risk of bleeding.

Feature tracking myocardial strain analysis in patients with bileaflet mitral valve prolapse: relationship with LGE and arrhythmias.

OBJECTIVES: Anatomical substrate and mechanical trigger co-act in arrhythmia's onset in patients with bileaflet mitral valve prolapse (bMVP). Feature tracking (FT) may improve risk stratification provided by cardiac magnetic resonance (CMR). The aim was to investigate differences in CMR and FT parameters in bMVP patients with and without complex arrhythmias (cVA and no-cVA). METHODS: In this retrospective study, 52 patients with bMVP underwent 1.5 T CMR and were classified either as no-cVA (n = 32; 12 males; 49.6 ± 17.4 years) or cVA (n = 20; 3 males; 44.7 ± 11.2 years), the latter group including 6 patients (1 male; 45.7 ± 12.7 years) with sustained ventricular tachycardia or ventricular fibrillation (SVT-FV). Twenty-four healthy volunteers (11 males, 36.2 ± 12.5 years) served as control. Curling, prolapse distance, mitral annulus disjunction (MAD), and late gadolinium enhancement (LGE) were recorded and CMR-FT analysis performed. Statistical analysis included non-parametric tests and binary logistic regression. RESULTS: LGE and MAD distance were associated with cVA with an odds ratio (OR) of 8.51 for LGE (95% CI 1.76, 41.28; p = 0.008) and of 1.25 for MAD (95% CI 1.02, 1.54; p = 0.03). GLS 2D (- 11.65 ± 6.58 vs - 16.55 ± 5.09 1/s; p = 0.04), PSSR longitudinal 2D (0.04 ± 1.62 1/s vs - 1.06 ± 0.35 1/s; p = 0.0001), and PSSR radial 3D (3.95 ± 1.97 1/s vs 2.64 ± 1.03 1/s; p = 0.0001) were different for SVT-VF versus the others. PDSR circumferential 2D (1.10 ± 0.54 vs. 0.84 ± 0.34 1/s; p = 0.04) and 3D (0.94 ± 0.42 vs. 0.69 ± 0.17 1/s; p = 0.04) differed between patients with and without papillary muscle LGE. CONCLUSIONS: CMR-FT allowed identifying subtle myocardial deformation abnormalities in bMVP patients at risk of SVT-VF. LGE and MAD distance were associated with cVA. KEY POINTS: • CMR-FT allows identifying several subtle myocardial deformation abnormalities in bMVP patients, especially those involving the papillary muscle. • CMR-FT allows identifying subtle myocardial deformation abnormalities in bMVP patients at risk of SVT and VF. • In patients with bMVP, the stronger predictor of cVA is LGE (OR = 8.51; 95% CI 1.76, 41.28; p = 0.008), followed by MAD distance (OR = 1.25; 95% CI 1.02, 1.54; p = 0.03).

In the midst of a dangerous intersection with unclear therapeutic strategies: a challenging case of severe aortic stenosis.

BACKGROUND: One out of seven patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) may be affected by transthyretin cardiac amyloidosis (ATTR-CA), mostly presenting with low-flow low-gradient AS with mildly reduced ejection fraction. The complex interaction of these two pathologies poses specific diagnostic and management challenges. The prognostic implications of this clinical intersection are not defined yet. Moreover, whether TAVR may have a prognostic benefit in ATTR-CA patients with symptomatic severe AS remains unclear, posing doubts on the best management strategy in this increasingly recognized subset of patients. CLINICAL CASE: We present a case of an 87-year old man with low-flow low-gradient severe AS, for whom a diagnosis of ATTR-CA was suspected based on clinical and echocardiographic criteria specific to coexisting AS and ATTR-CA. The diagnosis was eventually confirmed by positive bone tracer scintigraphy imaging. Following in-depth Heart team discussion, integrating frailty and prognostic information from combined cardiomyopathy states, a decision was made to manage the patient's severe AS conservatively. CONCLUSION: In the presented case, we deemed the natural history of ATTR-CA amyloidosis to negatively affect both the patient' prognosis and procedural risk, adversing TAVR indication despite symptomatic severe AS. No clear evidence is currently available to guide decision making in this setting, advocating for prospective studies to clarify if TAVR may have a prognostic benefit in ATTR-CA - and which ATTR-CA - patients.

S-ICD lead dislodgement in a young isometric athlete: A rare complication.

The subcutaneous implantable cardioverter defibrillator (S-ICD) is an alternative to transvenous ICD in patients who do not need cardiac pacing. We report the case of a young isometric athlete who received S-ICD for primary prevention of sudden death. Lead dislodgement and myopotential noise oversensing during isometric training led to inappropriate shock, and a surgical revision was performed. During the procedure, strong fibrous adhesions were found, requiring polytetrafluoroethylene dilator sheaths. The S-ICD was finally reimplanted. Despite continued isometric training, no more myopotential oversensing occurred after 1-year follow-up. The present case highlights the possible higher risks of lead complication in an isometric athlete and the uncommon effort in removing an old-generation subcutaneous defibrillator lead.

Incidental diagnosis of four pulmonary arteriovenous fistulas during patent foramen ovale closure: a case report.

Cryptogenic cerebral ischemia in young patients is commonly ascribed to paradoxical embolism. We report the clinical case of a young patient with cryptogenic stroke and a patent foramen ovale, undergoing percutaneous closure of atrial septal defect. Contrast transoesophageal echocardiography at the end of the procedure demonstrated massive late residual right-to-left shunt, due to the coexistence of pulmonary arteriovenous fistulas that were subsequently closed. Routinary adoption of contrast transoesophageal echocardiography at the end of patent foramen ovale closure interventions may be useful to detect early and late residual shunts. Late residual shunts may be due to pulmonary fistulas, a well-known risk factor for recurrent thromboembolic events.

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.

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.

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.

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.

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.

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.

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.

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.

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.