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.

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.

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.

Provisional Circulatory Support with Extracorporeal Membrane Oxygenation during Ventricular Tachycardia Ablation in Intermediate Risk Patients: A Case Series.

Background: Cardiogenic shock with acute hemodynamic decompensation may be one of the most serious risks in patients affected by ventricular tachycardia (VT). Its proper identification may have important implications in terms of pharmacological management, as might procedural planning in case of patients undergoing catheter ablation. Methods: We describe a case series of patients with provisional strategies for circulatory support in VT ablation, including the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) and vascular accesses in the electrophysiology lab but no initial ECMO activation due to an estimated intermediate pre-procedural risk from the case-series population. Results: In total, 10 patients (mean age 70 ± 11 years old, 9 males) with severe cardiomyopathy were admitted for incessant ventricular arrhythmia episodes, further diagnosis, and therapy planning; 1/10 patients (10%), documenting a PAINESD score of 14, underwent VA-ECMO cannulation due to electromechanical dissociation. All 10 patients were discharged alive. Conclusions: A pre-defined strategy before VT ablation is crucial. In our case series, the use of provisional circulatory support with VA-ECMO during incessant ablation of ventricular arrhythmia was a safe and winning alternative to upfront strategies.

Prognostic significance of electrophysiological study in drug-induced type-1 Brugada syndrome: a brief systematic review.

BACKGROUND: Risk stratification in drug-induced type-1 Brugada syndrome (BrS) patients is challenging. The role of electrophysiological study (EPS) is debated as the majority of drug-induced type-1 BrS patients would not be studied according to the latest recommendations. METHODS: A complete systematic literature search was performed to gauge the EPS role in this population. Three subgroups were defined: positive-EPS group, negative-EPS group, no-EPS group. RESULTS: Among 1318 drug-induced type-1 BrS patients, no significant difference in the incidence rate of arrhythmic events was observed between groups (I2 = 45%, P for subgroup difference = 0.10) during a mean follow-up of 5.1 years, also considering symptomatic status. CONCLUSION: In long-term follow-up of drug-induced type-1 BrS patients, EPS does not seem to aid prognostic stratification.

Takotsubo Syndrome and Gender Differences: Exploring Pathophysiological Mechanisms and Clinical Differences for a Personalized Approach in Patient Management.

Takotsubo syndrome (TTS), also known as the broken-heart syndrome, is a reversible condition typically observed in female patients presenting for acute coronary syndromes (ACS). Despite its increasing incidence, TTS often remains undiagnosed due to its overlap with ACS. The pathophysiology of TTS is complex and involves factors such as coronary vasospasm, microcirculatory dysfunction, increased catecholamine levels, and overactivity of the sympathetic nervous system. Diagnosing TTS requires a comprehensive approach, starting with clinical suspicion and progressing to both non-invasive and invasive multimodal tests guided by a specific diagnostic algorithm. Management of TTS should be personalized, considering potential complications, the presence or absence of coronary artery disease (CAD), diagnostic test results, and the patient's clinical course. The current data primarily derive from case series, retrospective analyses, prospective registries, and expert opinions. In recent years, there has been growing recognition of gender differences in the pathophysiology, presentation, and outcomes of TTS. This review provides an updated overview of gender disparities, highlighting the importance of tailored diagnostic and management strategies.

Aspirin in Primary Prevention: Looking for Those Who Enjoy It.

Based on a wealth of evidence, aspirin is one of the cornerstones of secondary prevention of cardiovascular disease. However, despite several studies showing efficacy also in primary prevention, an unopposed excess risk of bleeding leading to a very thin safety margin is evident in subjects without a clear acute cardiovascular event. Overall, the variability in recommendations from different scientific societies for aspirin use in primary prevention is a classic example of failure of simple risk stratification models based on competing risks (atherothrombosis vs. bleeding), perceived to be opposed but intertwined at the pathophysiological level. Notably, cardiovascular risk is dynamic in nature and cannot be accurately captured by scores, which do not always consider risk enhancers. Furthermore, the widespread use of other potent medications in primary prevention, such as lipid-lowering and anti-hypertensive drugs, might be reducing the benefit of aspirin in recent trials. Some authors, drawing from specific pathophysiological data, have suggested that specific subgroups might benefit more from aspirin. This includes patients with diabetes and those with obesity; sex-based differences are considered as well. Moreover, molecular analysis of platelet reactivity has been proposed. A beneficial effect of aspirin has also been demonstrated for the prevention of cancer, especially colorectal. This review explores evidence and controversies concerning the use of aspirin in primary prevention, considering new perspectives in order to provide a comprehensive individualized approach.

Polymorphonuclear neutrophils and instability of the atherosclerotic plaque: a causative role?

OBJECTIVE: The aim of this review is to examine the role of polymorphonuclear neutrophils (PMNs) in the evolution of atherosclerosis. INTRODUCTION: While the role of PMNs in the evolution of atherosclerosic process has failed until recently to attract much attention, a body of research carried out over the last decade has disclosed the unexpectedly complex behavior of these cells, unraveling an unexpected key role for PMNs in the onset and progression of atheroma. METHODS: A PubMed database search was performed for studies providing evidences on the role of PMNs in the development and progression of atherosclerotic lesion. RESULTS AND CONCLUSIONS: Activated PMNs were shown to produce and release reactive oxygen species, inflammatory leukotrienes and proteolytic lysosomal enzymes, directly inducing vascular damage. Activated PMNs also secrete myeloperoxidase, involved in lipoprotein oxidation. PMNs have a finite lifespan and typically die through apoptosis, which thus represents a counter-regulatory mechanism limiting the toxic potential of these short-lived, terminally differentiated cells. Dysregulation of this process probably contributes to the pathogenesis and progression of several inflammatory diseases. Moreover, high circulating levels of PMN-platelet aggregates have been reported in patients with clinical atherosclerosis, and recent studies suggest that these aggregates may play a role in vascular response to injury. It has been suggested that this heterotypic interaction between platelets and leukocytes might represent a link between hemostasis/thrombosis and the inflammatory response.

Speckle-tracking echocardiography: state of art and its applications.

Echocardiographic evaluation of left ventricular ejection fraction (LVEF) provides important information regarding both myocardial function and prognosis. This parameter presents various limitations and does not allow early detection of myocardial dysfunction. LVEF may be related to hemodynamic load, geometric assumptions, to image quality, and it does not reflect myocardial contractility. It has been hypothesized that speckle tracking echocardiography (STE) may allow overcoming such limits. STE through the measurement of strain and strain rate, which detect myocardial deformation, allows earlier identification of myocardial dysfunction in different settings both in presence of systolic and diastolic dysfunction, helps to predict left ventricular remodeling after acute myocardial infarction (AMI), and helps to decide the timing of surgery in asymptomatic severe valvular heart disease which is still a problematic issue. Increasingly interest regards the role of STE for the assessment of cardiomyopathies, myocarditis, and pulmonary hypertension. STE may be applied to the evaluation of systolic and diastolic dysfunction. STE is useful in all conditions in which cardiac dysfunction is not still overt, but a subclinical involvement is undoubtedly present such as in presence of cardiovascular risk factors and in cardio-oncology at earlier stages. It has been confirmed its role in predicting left ventricular remodeling after AMI which represents an important prognostic datum and in deciding the timing of surgery in asymptomatic valvular diseases. STE is an important tool to detect myocardial impairment even at earlier stages. 3DSTE and layer-specific strain represent promising fields of clinical application of STE.

Long-Term Outcomes of Transvenous Lead Extraction: A Comparison in Patients with or without Infection from the Italian Region with the Oldest Population.

BACKGROUND: The gold standard for the treatment of cardiac implantable electronic devices (CIEDs)-related infection and lead malfunction is transvenous lead extraction (TLE). To date, the risk of mortality directly related to TLE procedures is relatively low, but data on post-procedural and long-term mortality are limited, even more in the aging population. METHODS: Consecutive patients with CIEDs who underwent TLE were retrospectively studied. The primary outcome was the endpoint of death, considering independent predictors of long-term clinical outcomes in the TLE aging population comparing patients with and without infection. RESULTS: One hundred nineteen patients (male 77%; median age 76 years) were included in the analysis. Eighty-two patients (69%) documented infection, and thirty-seven (31%) were extracted for a different reason. Infected patients were older (80 vs. 68 years, p-value > 0.001) with more implanted catheters (p-value < 0.001). At the last follow-up (FU) available (median FU 4.1 years), mortality reached 37% of the patient population, showing a statistically significant difference between infected versus non-infected groups. At univariable analysis, age at TLE, atrial fibrillation, and anemia remained significant correlates of mortality; at multivariable analysis, only patients with anemia and atrial fibrillation have a 2.3-fold (HR 2.34; CI 1.16-4.75) and a 2.5-fold (HR 2.46; CI 1.33-4.54) increased rate of death, respectively. CONCLUSION: Our long-term data showed that aging patients who underwent TLE for CIED-related infection exhibit a high mortality risk during a long-term follow-up, potentially leading to a rapid and effective procedural approach in this patient population.

Duration of dual antiplatelet therapy and subsequent monotherapy type in patients undergoing drug-eluting stent implantation: a network meta-analysis.

AIMS: To compare the safety and efficacy of very short (≤3 months), short (6 months), standard (12 months), and extended (>12 months) dual antiplatelet therapy (DAPT), and of subsequent monotherapies, after coronary drug-eluting stent (DES) implantation. METHODS AND RESULTS: Twenty-two randomized control trials (n = 110 059 patients/year) were selected and included in a Bayesian network meta-analysis. The primary efficacy endpoint (PEP) was a composite of cardiac death, myocardial infarction (MI), and stent thrombosis (ST), with each of the components of the PEP being a secondary efficacy endpoint. The primary safety endpoint was major bleeding rate. Compared to standard, we found a lower rate of MI [odds ratio (OR) 0.56, 95% confidence interval (CI) 0.44-0.77] in extended, a lower rate of major bleeding (OR 0.61, 95% CI 0.39-0.87) in very short, and a lower rate of any bleeding (OR 0.61, 95% CI 0.38-0.90) in short DAPT. All DAPT durations were comparable regarding the secondary efficacy endpoints. Very short DAPT followed by P2Y12 inhibition was the treatment of choice to reduce both major bleeding and MI. In the ACS subgroup, extended DAPT (as compared to standard) reduced PEP and ST rates (but not MIs). CONCLUSION: The efficacy of short and very short is comparable with that of standard DAPT after DES implantation, whereas extended DAPT reduces MI rate. Very short DAPT is associated with lower haemorrhagic events and, followed by a P2Y12 inhibitor monotherapy, should be preferred in order to pursue a trade-off between major bleeding and ischaemic events.

Syncope in hypertrophic cardiomyopathy (part I): An updated systematic review and meta-analysis.

AIMS: To describe the proportion of patients with syncope among those affected by hypertrophic cardiomyopathy (HCM) and the relevance of syncope as risk factor for sudden cardiac death and life-threatening arrhythmic events. METHOD AND RESULTS: Systematic review of original articles that assessed syncope in HCM patients. Literature search of PubMed including all English publications from 1973 to 2021.We found 57 articles for a total of 21.791 patients; of these, 14 studies reported on arrhythmic events in the follow-up. Syncope was reported in 15.8% (3.452 of 21.791) patients. It was considered unexplained in 91% of cases. Life-threatening arrhythmic events occurred in 3.6% of non-syncopal patients and in 7.7% of syncopal patients during a mean follow-up of 5.6 years. A relative risk of 1.99 (95%CI 1.39 to 2.86) was estimated for syncope patients by the random effect model using Haldane continuity correction for 0 events. CONCLUSIONS: In the current practice, the cause of syncope remained unexplained in most patients affected by HCM. The management of patients seems mainly driven by risk stratification rather than identification of the aetiology of syncope. There is a need of precise instructions how to apply the recommendations of current guidelines to this disease, which tests are indicated and how to interpret their findings. The protocol was registered in Prospero (ID: 275963).

[Bileaflet mechanical valve dysfunction related to fibrous pannus: the role of cine-fluoroscopy]. / Disfunzione di protesi valvolare meccanica bileaflet da panno fibroso: non dimenticare la cine-fluoroscopia!

We report the case of a 72-year-old female patient admitted for worsening heart failure. The patient had undergone aortic valve replacement with a mechanical prosthesis 28 years before and since then she had several acute heart failure episodes, with a progressive increase in transprosthetic gradients, without identifying a specific cause.We describe the diagnostic tools used to reach a diagnosis, with particular emphasis on the use of cine-fluoroscopy that allowed to make the decisively diagnosis of prosthetic valve dysfunction, subsequently confirmed by cardiac computed tomography (CT). By cine-fluoroscopy, a widespread, easy, low-cost, and safe tool (no need for medium contrast and low radiation dose), it is possible to precisely define the function of the valve leaflets and measure their opening and closing angles, comparing them to the specific reference angles. To make the correct diagnosis we also performed a cardiac CT demonstrating a sub-aortic fibrous pannus. However, although cardiac CT is highly accurate for the identification of valve leaflet neoformations and abnormalities and for the discrimination between thrombotic formations and fibrous pannus, it is burdened by high costs, use of contrast medium, and limited available dedicated devices.

Sport practice in hypertrophic cardiomyopathy: running to stand still?

During the last decades, the practice of sport and hypertrophic cardiomyopathy (HCM) were considered as incompatible, since evidence was not sufficient to gauge the risk associated to repeat and/or vigorous exercise across the spectrum of HCM. Additionally, it was acknowledged thatrisk stratification tools developed for HCM were not derived from athlete cohorts. Recent epidemiological studies focused on HCM both in the general population and in athletes, however, have de-emphasized the contribution of this condition to the risk of sport-associated sudden death, supporting the possibility of allowing the practice of some sports, even at professional level, for certain low-risk HCM categories. We hereby analyze the complex interaction of vigorous and continuative exercise with HCM, revising the available evidence for sports eligibility in HCM, the challenges and limitations of shared decision-making, as well as the potential harms and benefits of a highly personalised exercise schedule in subjects diagnosed with this complex disease.

Interpretation of elevated high-sensitivity cardiac troponin I in elite soccer players previously infected by severe acute respiratory syndrome coronavirus 2.

OBJECTIVES: To clarify the meaning of elevated cardiac troponin in elite soccer athletes previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and screened for cardiovascular involvement in the wake of competitive sport resumption. METHODS: We designed a retrospective cohort study with the collaboration of two Italian Serie A teams. Soccer players from both rosters (58 athletes) were systematically analysed. For every SARS-CoV-2 positive athlete, the Italian Soccer Federation protocol requested full blood tests including high-sensitivity cardiac troponin I (hs-cTnI), along with a complete cardiovascular examination. We extended the analysis to SARS-CoV-2 negative athletes. RESULTS: A total of 13/58 players (22.4%) suffered from SARS-CoV-2infection: all had a negative cardiovascular examination and 2/13 (15%) showed increased hs-cTnI values (120.8 pg/ml and 72,6 pg/ml, respectively; upper reference level 39.2 pg/ml), which did not track with inflammatory biomarkers. Regarding the 45/58 (77.6%) non infected athletes, a slight increase in hs-cTnI was observed in 2 (4.5%) subjects (values: 61 pg/ml and 75 pg/ml respectively). All hs-cTnI positive athletes (4/58, 7%) underwent cardiac magnetic resonance (CMR), that excluded any cardiac injury. CONCLUSIONS: In our retrospective study, SARS-CoV-2 infection in elite soccer athletes was not associated to clinical or biomarkers abnormalities. Increased hs-cTnI was rare and not significantly associated with previous SARS-COV2 infection nor with pathological findings at CMR, albeit elevated hs-cTnI was numerically more prevalent in the infected group.

May standard basal echocardiogram allow to obtain predictors of asymptomatic cardiac dysfunction in alcoholics?

BACKGROUND: Long-lasting heavy alcohol intake has been progressively recognized as a leading cause of nonischemic dilated cardiomyopathy, involving 10% of all people who use alcohol. It is of huge importance to identify the earliest markers of this dysfunction and it is known that the newest echocardiographic techniques such as speckle tracking may allow to do it. In this study we investigated if standard basal echocardiogram features allow to obtain predictors of asymptomatic cardiac dysfunction in alcoholics. METHODS: A population of 80 consecutive asymptomatic alcoholics was enrolled. None presented history, signs or symptoms of cardiovascular disease. All of them underwent a conventional transthoracic monobidimensional and doppler echocardiography. RESULTS: Our cohort did not present echocardiographic findings of increased left ventricular sizes, mass or relative wall thickness. Hence, a significant rate of systolic dysfunction was not found. Furthermore, statistical analysis displayed an inverse relationship between alcohol consumption and systolic pulmonary arterial pressure as well as between alcohol abuse and left atrium enlargement. This may be explained by a potential vasodilator mechanism occurring in the earliest stages of alcohol intake. On the contrary, a positive correlation with the E/A ratio was found, and this might be ascribed to state of high cardiac output determined by alcohol abuse. There were modes sex-related differences. CONCLUSIONS: This study has demonstrated that standard echocardiography may allow to predict cardiac dysfunction in asymptomatic alcoholics, and sex-related differences may be identified in this regard. These data need to be confirmed by further studies involving larger population.

[Management of cardiogenic shock: a proposal for a shared protocol]. / Gestione dello shock cardiogeno: una proposta di percorso integrato.

Cardiogenic shock (CS) is a complex and relatively rare disease. Whilst its mortality remains unacceptably high, a multidisciplinary approach based on pre-established and shared protocols may improve prognosis and ensure appropriate resource allocation. Comprehensive hemodynamic assessment and monitoring as well as tailored, goal-directed medical therapy are part of an optimal management. Moreover, mechanical support devices may be helpful as they sustain hemodynamics to a greater extent as compared to inotropes and vasopressors, while lacking their cardiotoxic effects. Therefore, they are increasingly used in CS patients. In 2019, a new protocol for the management of patients with CS was adopted at the Ospedale Policlinico San Martino (HSM) in Genoa, Italy. Following in the footsteps of similar international experiences, the HSM protocol aims at streamlining the management of these high-risk patients improving the cooperation among healthcare specialists, and also addressing the key issues of mechanical support device implantation and appropriate referral for palliative care.