Ischaemic heart disease in patients with cancer.

Cardiologists are encountering a growing number of cancer patients with ischaemic heart disease (IHD). Several factors account for the interrelationship between these two conditions, in addition to improving survival rates in the cancer population. Established cardiovascular (CV) risk factors, such as hypercholesterolaemia and obesity, predispose to both IHD and cancer, through specific mechanisms and via low-grade, systemic inflammation. This latter is also fuelled by clonal haematopoiesis of indeterminate potential. Furthermore, experimental work indicates that IHD and cancer can promote one another, and the CV or metabolic toxicity of anticancer therapies can lead to IHD. The connections between IHD and cancer are reinforced by social determinants of health, non-medical factors that modify health outcomes and comprise individual and societal domains, including economic stability, educational and healthcare access and quality, neighbourhood and built environment, and social and community context. Management of IHD in cancer patients is often challenging, due to atypical presentation, increased bleeding and ischaemic risk, and worse outcomes as compared to patients without cancer. The decision to proceed with coronary revascularization and the choice of antithrombotic therapy can be difficult, particularly in patients with chronic coronary syndromes, necessitating multidisciplinary discussion that considers both general guidelines and specific features on a case by case basis. Randomized controlled trial evidence in cancer patients is very limited and there is urgent need for more data to inform clinical practice. Therefore, coexistence of IHD and cancer raises important scientific and practical questions that call for collaborative efforts from the cardio-oncology, cardiology, and oncology communities.

Athletes and suspected catecholaminergic polymorphic ventricular tachycardia: Awareness and current knowledge.

INTRODUCTION: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a cardiac inherited arrhythmogenic disease potentially leading to sudden cardiac death that is determined by electrical instability exacerbated by acute adrenergic tone. METHODS AND RESULTS: Despite its life-threatening nature, CPVT remains potentially unnoticed since diagnosis may be difficult especially in apparently healthy athletes. This review summarizes current knowledge and shortcomings of CPVT, focusing on genetics, arrhythmic mechanisms, sport preparticipation screening, and current recommendations. CONCLUSIONS: The paper captures the importance of CPVT athletes regarding the necessity of risk stratification, as well as the importance of maintaining a healthy lifestyle.

Direct Oral Anticoagulants for Cancer-Associated Venous Thromboembolism.

PURPOSE OF REVIEW: To present the randomized controlled trial (RCT) evidence and highlight the areas of uncertainty regarding direct oral anticoagulants (DOAC) for cancer-associated venous thromboembolism (CAT). RECENT FINDINGS: In the last years, four RCTs have shown that rivaroxaban, edoxaban, and apixaban are at least as effective as low-molecular-weight heparin (LMWH) for the treatment of both incidental and symptomatic CAT. On the other hand, these drugs increase the risk of major gastrointestinal bleeding in patients with cancer at this site. Another two RCTs have demonstrated that apixaban and rivaroxaban also prevent CAT in subjects at intermediate-to-high risk commencing chemotherapy, albeit at the price of higher likelihood of bleeding. By contrast, data are limited about the use DOAC in individuals with intracranial tumors or concomitant thrombocytopenia. It is also possible that some anticancer agents heighten the effects of DOAC via pharmacokinetic interactions, up to making their effectiveness-safety profile unfavorable. Leveraging the results of the aforementioned RCTS, current guidelines recommend DOAC as the anticoagulants of choice for CAT treatment and, in selected cases, prevention. However, the benefit of DOAC is less defined in specific patient subgroups, in which the choice of DOAC over LMWH should be carefully pondered.

Dual Antiplatelet Therapy with 3rd Generation P2Y12 Inhibitors in STEMI Patients: Impact of Body Mass Index on Loading Dose-Response.

PURPOSE: This study aims to assess the association between body mass index (BMI) and platelet reactivity in STEMI patients treated with oral 3rd generation P2Y12 inhibitors. METHODS: Overall, 429 STEMI patients were enrolled in this study. Patients were divided into two groups according to BMI (BMI < 25 vs ≥ 25 kg/m2). A propensity score matching (1:1) was performed to balance potential confounders in patient baseline characteristics. Platelet reactivity was assessed by VerifyNow at baseline and after 3rd generation P2Y12 inhibitor (ticagrelor or prasugrel) loading dose (LD). Blood samples were obtained at baseline (T0), 1 h (T1), 2 h (T2), 4-6 h (T3), and 8-12 h (T4) after the LD. High on-treatment platelet reactivity (HTPR) was defined as a platelet reactivity unit value ≥ 208 units. RESULTS: After propensity score matching, patients with BMI ≥ 25 had similar values of baseline platelet reactivity, while they had higher level of platelet reactivity at 1 and 2 h after the LD and higher rate of HRPT. Furthermore, multivariate analysis demonstrated that BMI ≥ 25 was an independent predictor of HTPR at 2 h (OR 2.01, p = .009). Conversely, starting from 4 h after the LD, platelet reactivity values and HRPT rates were comparable among the two study groups. CONCLUSIONS: A BMI ≥ 25 kg/m2 is associated with delayed pharmacodynamic response to oral 3rd generation P2Y12 inhibitor LD, and it is a strong predictor of HTPR in STEMI patients treated by dual antiplatelet therapy with ticagrelor or prasugrel.

Guided versus standard antiplatelet therapy in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis.

BACKGROUND: Whether guided selection of antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI) is effective in improving outcomes compared with standard antiplatelet therapy remains controversial. We assessed the safety and efficacy of guided versus standard selection of antiplatelet therapy in patients undergoing PCI. METHODS: For this systematic review and meta-analysis, from Aug 20 to Oct 25, 2020, we searched MEDLINE (via PubMed), Cochrane, Embase, and Web of Science databases for randomised controlled trials and observational studies published in any language that compared guided antiplatelet therapy, by means of platelet function testing or genetic testing, versus standard antiplatelet therapy in patients undergoing PCI. Two reviewers independently assessed study eligibility, extracted the data, and assessed risk of bias. Risk ratios (RRs) and 95% CIs were used with random-effects or fixed-effect models according to the estimated heterogeneity among studies assessed by the I2 index. Coprimary endpoints were trial-defined primary major adverse cardiovascular events and any bleeding. Key secondary endpoints were all-cause death, cardiovascular death, myocardial infarction, stroke, definite or probable stent thrombosis, and major and minor bleeding. This study is registered with PROSPERO (CRD42021215901). FINDINGS: 3656 potentially relevant articles were screened. Our analysis included 11 randomised controlled trials and three observational studies with data for 20 743 patients. Compared with standard therapy, guided selection of antiplatelet therapy was associated with a reduction in major adverse cardiovascular events (RR 0·78, 95% CI 0·63-0·95, p=0·015) and reduced bleeding, although not statistically significant (RR 0·88, 0·77-1·01, p=0·069). Cardiovascular death (RR 0·77, 95% CI 0·59-1·00, p=0·049), myocardial infarction (RR 0·76, 0·60-0·96, p=0·021), stent thrombosis (RR 0·64, 0·46-0·89, p=0·011), stroke (RR 0·66, 0·48-0·91, p=0·010), and minor bleeding (RR 0·78, 0·67-0·92, p=0·0030) were reduced with guided therapy compared with standard therapy. Risks of all-cause death and major bleeding did not differ between guided and standard approaches. Outcomes varied according to the strategy used, with an escalation approach associated with a significant reduction in ischaemic events without any trade-off in safety, and a de-escalation approach associated with a significant reduction in bleeding, without any trade-off in efficacy. INTERPRETATION: Guided selection of antiplatelet therapy improved both composite and individual efficacy outcomes with a favourable safety profile, driven by a reduction in minor bleeding, supporting the use of platelet function or genetic testing to optimise the choice of agent in patients undergoing PCI. FUNDING: None.

Network meta-analysis of medical therapy efficacy in more than 90,000 patients with heart failure and reduced ejection fraction.

BACKGROUND: Following the availability of new drugs for chronic heart failure (HF) with reduced ejection fraction (HFrEF), we sought to provide an updated and comparative synthesis of the evidence on HFrEF pharmacotherapy efficacy. METHODS: We performed a Bayesian network meta-analysis of phase 2 and 3 randomized controlled trials (RCTs) of medical therapy in HFrEF patient cohorts with more than 90% of the participants with left ventricular ejection fraction less than 45% and all-cause mortality reported. RESULTS: Sixty-nine RCTs, accounting for 91,741 subjects, were evaluated. The step-wise introduction of new drugs progressively decreased the risk of all-cause death, up to reaching a random-effects hazard ratio (HR) of 0.43 (95% credible intervals [CrI] 0.27-0.63) with beta blockers (BB), angiotensin-converting enzyme inhibitors (ACEi), and mineralocorticoid receptor antagonist (MRA) versus placebo. The risk was further reduced by adding sodium-glucose cotransporter-2 inhibitors (SGLT2i; HR 0.38, 95% CrI 0.22-0.60), ivabradine (HR 0.39, 95% CrI 0.21-0.64), or vericiguat (HR 0.40, 95% CrI 0.22-0.65) to neurohormonal inhibitors, and by angiotensin receptor-neprilysin inhibitor (ARNI), BB, and MRA (HR 0.36, 95% CrI 0.20-0.60). In a sensitivity analysis considering the ARNI and non-ARNI subgroups of SGLT2i RCTs, the combination SGLT2i + ARNI + BB + MRA was associated with the lowest HR (0.28, 95% CrI 0.16-0.45 vs. 0.40, 95% CrI 0.24-0.60 for SGLT2i + BB + ACEi + MRA). Consistent results were obtained in sensitivity analyses and by calculating surface under the cumulative ranking area, as well as for cardiovascular mortality (information available for 56 RCTs), HF hospitalization (45 RCTs), and all-cause hospitalization (26 RCTs). CONCLUSIONS: Combination medical therapy including neurohormonal inhibitors and newer drugs, especially ARNI and SGLT2i, confers the maximum benefit with regard to HFrEF prognosis.

Mechanical circulatory support in patients with cardiogenic shock not secondary to cardiotomy: a network meta-analysis.

To compare the efficacy and safety of different mechanical circulatory support (MCS) devices in CS. A total of 24 studies (7 randomized controlled trials-RCTs-and 17 non-RCTs) involving 11,117 patients were entered in a Bayesian network meta-analysis. The primary endpoint was 30-day mortality. Secondary endpoints were stroke and bleeding (requiring transfusion and/or intracranial and/or fatal). Compared with no MCS, extra-corporeal membrane oxygenation (ECMO) reduced 30-day mortality when used both alone (OR 0.37, 95% CrI 0.15-0.90) and together with the micro-axial pump Impella (OR 0.13, 95% CrI 0.02-0.80) or intra-aortic balloon pump (IABP) (OR 0.19, 95% CrI 0.05-0.63), although the relevant articles were affected by significant publication bias. Consistent results were obtained in a sensitivity analysis including only studies of CS due to myocardial infarction. After halving the weight of studies with a non-RCT design, only the benefit of ECMO + IABP on 30-day mortality was maintained (OR 0.22, 95% CI 0.057-0.76). The risk of bleeding was increased by TandemHeart (OR 13, 95% CrI 3.50-59), Impella (OR 5, 95% CrI 1.60-18), and IABP (OR 2.2, 95% CrI 1.10-4.4). No significant differences were found across MCS strategies regarding stroke. Although limited by important quality issues, the studies performed so far indicate that ECMO, especially if combined with Impella or IABP, reduces short-term mortality in CS. MCS increases the hazard of bleeding.

Myocardial bridge evaluation towards personalized medicine: study design and preliminary results of the RIALTO registry.

Myocardial bridge (MB) is the most frequent inborn coronary artery variant in which a portion of the myocardium overlies an epicardial coronary artery segment. Although MB has long been considered a benign entity, a growing body of evidence has suggested its association with angina and adverse cardiac events. However, to date, no data on long-term prognosis are available, nor on therapies improving cardiovascular outcomes. We are currently conducting an ambispective, observational, multicentre, study in which we enrol patients with a clinical indication to undergo coronary angiography (CA) and evidence of MB, aiming to describe the incidence of symptoms and cardiovascular events at baseline and at long-term follow-up (FUP). The role of invasive full-physiology assessment in modifying the discharge therapy and eventually the perceived quality of life and the incidence of major cardiovascular events will be analysed. Basal clinical-instrumental data of eligible and consenting patients have been acquired after CA; FUP was performed 6, 12, and 24 months after the angiographic diagnosis of MB. The primary endpoint of the study is the incidence of major adverse cardiovascular events (MACE), defined as the composite of cardiac death, myocardial infarction, cardiac hospitalization, and target vessel revascularization; the secondary endpoints are the rate of patients with Seattle Angina Questionnaire (SAQ) summary score <70 and the incidence of MACE in patients undergoing invasive intracoronary assessment. Among patients undergone FUP visits, we recorded 31 MACE at 6 months (11.6%), 16 MACE at 12 months (6.5%), and 26 MACE at 24 months (13.5%). The rate of patients with SAQ <70 is 18.8% at 6 months, 20.6% at 12 months, and 21.8% at 24 months. To evaluate the prognostic role of invasive intracoronary assessment, we compared MB patients who underwent only angiographic evaluation (Angio group) to those who underwent acetylcholine (ACH) provocative test with indication to calcium-channel blockers (CCBs) at discharge (Angio + ACH + CCBs group) and those who underwent functional assessment with fractional flow reserve (FFR) with indication to beta-blockers (BBs) at discharge (Angio + FFR + BBs group). After 2 years of FUP, the rate of MACE was significantly reduced in both Angio + ACH + CCBs group (6 vs. 25%, P = 0.029) and Angio + FFR + BBs group (3 vs. 25%, P = 0.005) compared with Angio group. The preliminary results of our study showed that MB may be a cause of angina and adverse cardiac events in patients referred to CA for suspected coronary artery disease (CAD). Full-physiology assessment unmasking MB-related ischaemia mechanisms, allowed to guide the treatment, personalizing the clinical management, improving the quality of life, and cardiovascular outcomes in patients with MB.

Antiplatelet therapy in patients with conservatively managed spontaneous coronary artery dissection from the multicentre DISCO registry.

AIMS: The role of antiplatelet therapy in patients with spontaneous coronary artery dissection (SCAD) undergoing initial conservative management is still a matter of debate, with theoretical arguments in favour and against its use. The aims of this article are to assess the use of antiplatelet drugs in medically treated SCAD patients and to investigate the relationship between single (SAPT) and dual (DAPT) antiplatelet regimens and 1-year patient outcomes. METHODS AND RESULTS: We investigated the 1-year outcome of patients with SCAD managed with initial conservative treatment included in the DIssezioni Spontanee COronariche (DISCO) multicentre international registry. Patients were divided into two groups according to SAPT or DAPT prescription. Primary endpoint was 12-month incidence of major adverse cardiovascular events (MACE) defined as the composite of all-cause death, non-fatal myocardial infarction (MI), and any unplanned percutaneous coronary intervention (PCI). Out of 314 patients included in the DISCO registry, we investigated 199 patients in whom SCAD was managed conservatively. Most patients were female (89%), presented with acute coronary syndrome (92%) and mean age was 52.3 ± 9.3 years. Sixty-seven (33.7%) were given SAPT whereas 132 (66.3%) with DAPT. Aspirin plus either clopidogrel or ticagrelor were prescribed in 62.9% and 36.4% of DAPT patients, respectively. Overall, a 14.6% MACE rate was observed at 12 months of follow-up. Patients treated with DAPT had a significantly higher MACE rate than those with SAPT [18.9% vs. 6.0% hazard ratios (HR) 2.62; 95% confidence intervals (CI) 1.22-5.61; P = 0.013], driven by an early excess of non-fatal MI or unplanned PCI. At multiple regression analysis, type 2a SCAD (OR: 3.69; 95% CI 1.41-9.61; P = 0.007) and DAPT regimen (OR: 4.54; 95% CI 1.31-14.28; P = 0.016) resulted independently associated with a higher risk of 12-month MACE. CONCLUSIONS: In this European registry, most patients with SCAD undergoing initial conservative management received DAPT. Yet, at 1-year follow-up, DAPT, as compared with SAPT, was independently associated with a higher rate of adverse cardiovascular events (ClinicalTrial.gov id: NCT04415762).

Coronary microvascular dysfunction beyond microvascular obstruction in ST-elevation myocardial infarction: Functional and clinical correlates.

OBJECTIVES: To retrospectively characterize clinical predictors and impact on left ventricular (LV) ejection fraction (EF) of microvascular dysfunction (MVD) beyond microvascular obstruction (MVO), in 49 consecutive patients (58 ± 11 years), with successfully treated ST-elevation myocardial infarction. METHODS: By myocardial contrast echocardiography, MVD was considered as myocardial segments with delayed/patchy opacification, while MVO as areas without any opacification. Both MVD and MVO were planimetered and expressed as percentage of total LV wall area. Patients were divided into tertiles of MVO: I (MVO 0%), II (MVO 4-17%), and III (MVO 18-38%) groups. Cardiac troponin T (cTnT) values obtained at admission and at peak were considered for analysis. RESULTS: MVD correlated inversely with EF in groups I and II (p = 0.025, p = 0.019, respectively), but not in group III. MVD was independently predicted by cTnT on admission (ß = 1.85; 95%CI = 0.46-3.24, p = 0.011) and female sex (ß for male sex = -14.46; 95% CI = -27.96-0.95), while MVO by anterior MI (ß = 0.57; 95% CI = 0.26-0.88, p = 0.008) and peak cTnT (ß = 0.97; 95%CI = 0.57-1.38, p < 0.001). Altogether, MVD plus MVO predicted EF (ß = -0.18; 95%CI = -0.28--0.07, p = 0.002). CONCLUSIONS: Even in patients with limited amount of MVO, EF may be impaired by MVD. MVO and MVD have different predictors, which probably reflect their different pathogenesis.

Atrial fibrillation and Alzheimer's disease: A conundrum.

During ageing, the prevalence of Alzheimer's disease (AD) and of cardiovascular disease CVD) increases. Our aim is to investigate the relationship between AD and CVD and its risk factors, with a view to explaining the underlying mechanisms of this association. This review is based on the material obtained via MEDLINE (PubMed), Embase and Clinical Trials databases, from January 1980 until May 2019. The search term used was "Alzheimer's disease", combined with "cardiovascular disease", "hypertension", "dyslipidaemia", "diabetes mellitus", "atrial fibrillation", "coronary artery disease", "heart valve disease", "heart failure". Out of the 1328 papers initially retrieved, 431 duplicates and 216 records in languages other than English were removed; thus, only 98 papers were included in our research material. We have found that AD and CVD are frequently associated, while both of them, alone may be considered deleterious to health, the study of their combination constitutes a clinical challenge. Further research will help to clarify the real impact of CVD and its risk factors on AD, in order to better comprehend the effects of subclinical and clinical cardiovascular diseases on the brain. It may be hypothesized that there are various mechanisms underlying the association between AD and CVD, the main ones being: hypoperfusion and emboli, atherosclerosis, furthermore in both the heart and brain of AD patients, amyloid deposits may be present, thus causing damage to these organs. We need to clarify the real impact of these underlying hypothesized mechanisms and to investigate gender issues.

Cardiovascular safety of the tyrosine kinase inhibitor nintedanib.

The intracellular tyrosine kinase inhibitor nintedanib has shown great efficacy for the treatment of idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases. However, the incidence rate of myocardial infarction (MI) among participants in landmark IPF trials was remarkable, peaking at 3/100 patient-years. Although subjects with IPF often have a high cardiovascular (CV) risk profile, the occurrence of MI in nintedanib-treated patients may not be fully explained by clustering of CV risk factors. Nintedanib inhibits the vascular endothelial growth factor, platelet-derived growth factor and fibroblast growth factor pathways, which play important roles in the biology of the atherosclerotic plaque and in the response of the heart to ischaemia. Hence, unwanted CV effects may partly account for nintedanib-related MI. We review the evidence supporting this hypothesis and discuss possible actions for a safe implementation of nintedanib in clinical practice, building on the experience with tyrosine kinase inhibitors acquired in cardio-oncology.

Brugada syndrome and syncope: a practical approach for diagnosis and treatment.

Syncope in patients with Brugada electrocardiogram pattern may represent a conundrum in the decision algorithm because incidental benign forms, especially neurally mediated syncope, are very frequent in this syndrome similarly to the general population. Arrhythmic syncope in Brugada syndrome typically results from a self-terminating sustained ventricular tachycardia or paroxysmal ventricular fibrillation, potentially leading to sudden cardiac death. Distinguishing syncope due to malignant arrhythmias from a benign form is often difficult unless an electrocardiogram is recorded during the episode. We performed a review of the existing literature and propose a practical approach for diagnosis and treatment of the patients with Brugada syndrome and syncope.

Implications of atrial fibrillation on the clinical course and outcomes of hospitalized COVID-19 patients: results of the Cardio-COVID-Italy multicentre study.

AIMS: To assess the clinical relevance of a history of atrial fibrillation (AF) in hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS AND RESULTS: We enrolled 696 consecutive patients (mean age 67.4 ± 13.2 years, 69.7% males) admitted for COVID-19 in 13 Italian cardiology centres between 1 March and 9 April 2020. One hundred and six patients (15%) had a history of AF and the median hospitalization length was 14 days (interquartile range 9-24). Patients with a history of AF were older and with a higher burden of cardiovascular risk factors. Compared to patients without AF, they showed a higher rate of in-hospital death (38.7% vs. 20.8%; P < 0.001). History of AF was associated with an increased risk of death after adjustment for clinical confounders related to COVID-19 severity and cardiovascular comorbidities, including history of heart failure (HF) and increased plasma troponin [adjusted hazard ratio (HR): 1.73; 95% confidence interval (CI) 1.06-2.84; P = 0.029]. Patients with a history of AF also had more in-hospital clinical events including new-onset AF (36.8% vs. 7.9%; P < 0.001), acute HF (25.3% vs. 6.3%; P < 0.001), and multiorgan failure (13.9% vs. 5.8%; P = 0.010). The association between AF and worse outcome was not modified by previous or concomitant use of anticoagulants or steroid therapy (P for interaction >0.05 for both) and was not related to stroke or bleeding events. CONCLUSION: Among hospitalized patients with COVID-19, a history of AF contributes to worse clinical course with a higher mortality and in-hospital events including new-onset AF, acute HF, and multiorgan failure. The mortality risk remains significant after adjustment for variables associated with COVID-19 severity and comorbidities.

Impact of bioprosthetic valve type on peri-procedural myocardial injury and mortality after transcatheter aortic valve replacement.

Peri-procedural myocardial injury (PPMI) is a common complication after transcatheter valve replacement (TAVR), often remaining clinically silent. The role of valve type on PPMI and the association between PPMI and mortality are still unclear. We sought to evaluate predictors and outcome of PPMI after TAVR, and the impact of self-expandable valve (SEV) vs. balloon-expandable valve (BEV) deployment on PPMI. Consecutive patients who underwent successful TAVR in a single-center from January 2014 to December 2019 were included. PPMI was defined according to a modified Valve Academic Research Consortium (VARC)-2 definition as a post-procedure elevation of troponin (with a peak value ≥ 15-times the upper-reference limit) < 72 h after TAVR. We included 596 patients, of whom 258 (43.3%) were men. Mean age was 83.4 ± 5.5 years. We deployed 368 (61.7%) BEV and 228 (38.3%) SEV. PPMI was observed in 471 (79.0%) patients. At multivariable analysis, SEV (OR 2.70, 95% CI 1.64-4.55, p < 0.001), creatinine clearance (OR 0.98, 95% CI 0.97-1.00, p = 0.011), and baseline ejection fraction (OR 1.05, 95% CI 1.02-1.07, p < 0.001) were independent predictors of PPMI; these findings were also confirmed using a propensity-weighted analysis. Thirty-day and 1-year all-cause mortality rates were 2.5% and 8.1%, respectively. No associations between PPMI and 30-day (p = 0.488) or 1-year (p = 0.139) all-cause mortality were found. Independent predictors of 30-day mortality were increasing EUROSCORE II (HR 1.16 per score point, 95% CI 1.08-1.19, p < 0.001) and life-threatening/major bleeding complications (HR 5.87, 95% CI 1.28-26.58, p = 0.019), whereas EUROSCORE II (HR 1.08, 95% CI 1.04-1.13, p = 0.031) and acute kidney injury (HR 2.59, 95% CI 1.20-5.35, p = 0.020) were related to 1-year mortality. PPMI is frequent after TAVR, but it does not affect 30-day or 1-year all-cause mortality. SEV implantation is associated with an increased frequency of PPMI.

The arrhythmogenic right ventricular cardiomyopathy in comparison to the athletic heart.

Intense exercise-induced right ventricular remodeling is a potential adaptation of cardiac function and structure. The features of the remodeling may overlap with those of a very early form of arrhythmogenic right ventricular cardiomyopathy (ARVC): at this early stage, it could be difficult to discriminate ARVC, from exercise-induced cardiac adaptation that may develop in normal individuals. The purpose of this paper is to discuss which exercise-induced remodeling may be a pathological or a physiological finding. A complete evaluation may be required to identify the pathological features of ARVC that would include potential risk of sudden cardiac death during sport or, to avoid the false diagnosis of ARVC. The most recent expert assessment of arrhythmogenic cardiomyopathy focuses on endurance athletes presenting with clinical features indistinguishable from ARVC.

Brugada syndrome and syncope: A systematic review.

INTRODUCTION: Distinguishing syncope due to malignant arrhythmias from an incidental benign form in Brugada syndrome (BrS) is often difficult. Through systematic literature review, we evaluated the role of syncope in predicting subsequent malignant arrhythmias in BrS. METHODS: A comprehensive literature search was performed on PubMed (MeSH search terms "Brugada syndrome" and "syncope"). Overall, 9 studies for a total of 1347 patients were included. Patients were stratified as affected by suspected arrhythmic syncope (SAS), undefined syncope (US) or neurally-mediated syncope (NMS). RESULTS: Overall, 15.7% of the 279 patients with SAS had malignant arrhythmic events during a mean follow-up of 67 months, corresponding to 2.8 events per 100/person year. At the same time, 7% of the 527 patients affected by US had malignant arrhythmias during a mean follow-up of 39 months, corresponding 2.2 events per 100/person year. Conversely, 0.7% of 541 patients with NMS had malignant arrhythmic events at follow-up, corresponding to 0.13 events per 100/person year (p = .0001 NMS versus SAS and US pooled). CONCLUSION: In BrS population, the risk of arrhythmic events in the follow-up may be stratified according to the clinical evaluation. The "relatively" low predictive value of the clinical diagnosis of SAS warrants for a more accurate multi-parametric assessment, to restrict the number of candidates for implantable cardioverter-defibrillator therapy.

Intracranial haemorrhages vs. stent thromboses with direct oral anticoagulant plus single antiplatelet agent or triple antithrombotic therapy: a meta-analysis of randomized trials in atrial fibrillation and percutaneous coronary intervention/acute coronary syndrome patients.

AIMS: To assess the efficacy-safety profile of dual antithrombotic therapy (DAT) including direct oral anticoagulant (DOAC) vs. triple antithrombotic therapy (TAT) in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: Randomized trials of AF patients with ACS/PCI, comparing DAT using DOACs against TAT, were selected. Overall, 11 161 studies were screened, 458 trials assessed, and four included, comprising 10 234 patients followed for a mean of 11 months. DAT compared to TAT resulted in significant reductions of trial-defined primary safety outcome [odds ratio (OR) 0.63, 95% confidence interval (CI) 0.50-0.79, number needed to treat (NNT) 17] and of thrombolysis in myocardial infarction (TIMI) major bleeding (OR 0.54, 95% CI 0.41-0.70, NNT 76) and in a numerical reduction of intracranial haemorrhage (OR 0.50, 95% CI 0.21-1.19, NNT 314), which became significant after exclusion of DOACs from TAT and vitamin K antagonist from DAT arms (OR 0.31, 95% CI 0.15-0.64). There were no significant differences in the risks of cardiovascular or any deaths or stroke, but with DAT, there was a numerical increase in myocardial infarctions (MIs) (OR 1.23, 95% CI 0.99-1.54, estimated NNT for an additional harmful outcome (NNTH) 151), which became significant in the ACS/PCI subgroup (OR 1.43, 95% CI 1.02-2.00), and a 60% significant increase in stent thrombosis risk (OR 1.60, 95% CI 1.02-2.52; NNTH 274). CONCLUSION: Dual antithrombotic therapy, compared to TAT, conferred a significantly reduced risk of overall bleeding but with a significant increase of stent thrombosis risk in the overall population and a significant 43% increase of MI in the ACS/PCI subgroup.

Long-Term Outcomes of Extent of Revascularization in Complex High Risk and Indicated Patients Undergoing Impella-Protected Percutaneous Coronary Intervention: Report from the Roma-Verona Registry.

OBJECTIVE: To investigate the effect of extent of revascularization in complex high-risk indicated patients (CHIP) undergoing Impella-protected percutaneous coronary intervention (PCI). BACKGROUND: Complete revascularization has been shown to be associated with improved outcomes. However, the impact of more complete revascularization during Impella-protected PCI in CHIP has not been reported. METHODS: A total of 86 CHIP undergoing elective PCI with Impella 2.5 or Impella CP between April 2007 and December 2016 from 2 high volume Italian centers were included. Baseline, procedural, and clinical outcomes data were collected retrospectively. Completeness of coronary revascularization was assessed using the British Cardiovascular Intervention Society myocardial jeopardy score (BCIS-JS) derived revascularization index (RI). The primary end-point was all-cause mortality. A multivariate regression model was used to identify independent predictors of mortality. RESULTS: All patients had multivessel disease and were considered unsuitable for surgery. At baseline, 44% had left main disease, 78% had LVEF ≤ 35%, and mean BCIS-JS score was 10±2. The mean BCIS-JS derived RI was 0.7±0.2 and procedural complications were uncommon. At 14-month follow-up, all-cause mortality was 10.5%. At follow-up, 67.4% of CHIP had LVEF ≥ 35% compared to 22.1% before Impella protected-PCI. Higher BCIS-JS RI was significantly associated with LVEF improvement (p=0.002). BCIS-JS RI of ≤ 0.8 (HR 0.11, 95% CI 0.01- 0.92, and p = 0.042) was an independent predictor of mortality. CONCLUSIONS: These results support the practice of percutaneous Impella use for protected PCI in CHIP. A more complete revascularization was associated with significant LVEF improvement and survival.

Role of Invasive and Non-invasive Imaging Tools in the Diagnosis and Optimal Treatment of Patients with Spontaneous Coronary Artery Dissection.

PURPOSE OF REVIEW: Spontaneous coronary artery dissection (SCAD) is a serious non-atherosclerotic disease, most frequently presenting as an acute coronary syndrome and affecting female patients. Considering that diagnosis of SCAD is often elusive, and its interventional treatment is associated to a higher rate of complications than obstructive atherosclerotic disease, we aim to review all the imaging tools currently available for the optimal diagnosis and treatment of this condition. RECENT FINDINGS: The developments in both invasive and non-invasive imaging alternatives to coronary angiography, such as intravascular ultrasound, optical coherence tomography, and computed coronary angiography, have largely contributed to appraise the epidemiology of SCAD, understand its causative pathophysiological mechanisms, and improve our ability to confirm doubtful cases of SCAD. Intracoronary imaging is also a valuable in deciding the best therapeutic approach and in guiding interventions in those patients requiring percutaneous treatment. Furthermore, non-invasive imaging is a key tool in ruling out significant extracoronary vascular abnormalities which frequently occur in patients with underlying conditions like fibromuscular dysplasia who develop SCAD. Main imaging tools employed in SCAD cases could have advantages and drawbacks. Focusing on different types of SCAD, operators should be able to choose the best imaging technique for diagnosis, management, and follow-up.