Abstract
Pathology of conduction tissue (CT) and relative arrhythmic manifestations in living subjects with cardiac amyloid (CA) have never been reported.
In 17 out of 45 consecutive patients with CA, a left ventricular (LV) endomyocardial biopsy included CT sections. Extensive clinical examination, non-invasive (resting ECG, Holter monitoring, echocardiography), and invasive cardiac studies (selective coronary angiography, LV angiography, and LV endomyocardial biopsy) were performed in all patients. Cardiac magnetic resonance (CMR) was performed in 12 of the 17 patients (70%). CT was identified by Aschoff-Monckeberg histologic criteria associated to positive immunostaining for HCN4. Degree of CT infiltration was defined as mild when ≤ 30% of CT area was replaced by fibrous tissue and Congo red+ material, moderate in 30–70% CT area involvement and severe in > 70% CT cell area replacement. CT infiltration was correlated with ventricular arrhythmias, echocardiographic LV maximal wall thickness (MWT) and type of amyloid protein identified by myocardial immunohistochemistry. CMR confirmed the presence of cardiac hypertrophy with preserved systolic function in all but one patient. LGE was present in all patients, predominantly with diffuse (5/11) or subendocardial (4/11) pattern compared to focal (2/11). In 7/11 patients T1 mapping sequences have been acquired; nT1 and ECV were increase in all patients (nT1: 1171 ± 61 ms; ECV: 59.9 ± 7.5%). Mild CT involvement was observed in 5 cases; moderate in 3; severe compromise in 9. CT involvement was associated with a parallel infiltration of CT artery. CT infiltration correlated with severity of arrhythmias (Spearman rho = 0.8, P < 0.001) but not with age, MWT or type of amyloid protein. In particular, major ventricular tachyarrhythmias requiring pharmacologic treatment or ICD implantation occurred in 7 patients with severe, 1 patient with moderate and none with mild CT infiltration. Pacemaker implantation was required in 3 patients with complete CT area replacement.
CA associated arrhythmias correlate with severity of CT infiltration. CT involvement is independent from type and severity of CA suggesting a variable affinity of amyloid protein to CT.
588 Acetylcholinesterase inhibitors: evaluation of potential positive cardiac effects in patients with Alzheimer's disease
Aims
Acetylcholinesterase inhibitors (AChE-Is) are used to improve cognitive functions in patients with Alzheimer's disease (AD). AChE-Is have miscellaneous effects on the cardiovascular system, partly explained by their vagotonic and anti-inflammatory properties. There is little evidence of reduction of cardiovascular diseases (CVDs) in patients chronically treated by AChE-Is. In this study we explored the potential role of AChE-Is in reducing cardiovascular events in patients with AD.
Methods and results
In this retrospective cohort study we enrolled AD patients treated by AChE-Is referred to the Neurology department of our institution. Patients’ caregivers with comparable age acted as control group. The primary outcome was a composite of cardiovascular events (cardiovascular death, acute myocardial infarction, coronary revascularization, stroke and/or transient ischaemic attack, hospitalizations for heart failure). Descriptive statistics, Kaplan-Meier time to event and univariate and multivariate Cox regression analysis were performed.
One hundred and four AD patients (Group 1) taking AChE-Is (50 Donepezil, 54 Rivastigmine) and 98 control subjects (Group 2) not taking AChE-Is were analyzed. The median duration of follow-up was 5 years. Baseline characteristics were comparable between the two groups except for: history atrial fibrillation (AF) (4% in Group 1 vs. 12% in Group 2, P = 0.032), family history of CVDs (17% in Group 1 vs. 30% in Group 2, P = 0.038), use of Aspirin (51% in Group 1 vs. 30% in Group 2, P = 0.002) and use of psychotropic drugs (significantly major in Group 1). A total of 34 events (9 [9%] in Group 1 and 25 [25%] in Group 2) occurred. Kaplan–Meier survival curves revealed significant higher rate of the composite outcome in Group 2 (log-rank: P = 0.021). General mortality and hospitalization for non-cardiovascular causes were not different between groups. At Cox regression univariate analysis, history of AF [HR 4.086 (95% IC 1.894–8.816)], higher age [HR 1.059 (95% IC 1.005–1.115)] and family history of CVDs [HR 2.045 (95% IC 1.004–4.167)] significantly increased while belonging to Group 1 [HR 0.428 (95% IR 0.198–0.927)] significantly reduced the risk of the composite outcome. Belonging to Group 1 [P-value 0.021 HR 0.335 (95% IC 0.132–0.849) and history of AF [P-value 0.032 HR 2.703 (95% IC 1.092–6.693) remained statistically significant after multivariate adjustment. In Group 1, dosage and type of AChE-I had no impact on the incidence of the composite outcome.
Conclusions
Our data show that the incidence of main cardiovascular events was lower in the group taking AChE-Is, compared to the control one. Therefore, the use of AChE-I appears to have a potential cardiovascular protective role. Further studies are needed to explore this protective role on a wider range of patients.
45 What bibliometric indicators should be used for the evaluation of individual researchers and biomedical journals?
Bibliometric indicators are now the cornerstone of biomedical researchers' assessments in their career progression paths (H-index, in particular, accepted as a yardstick for research output in most universities and research centers). Furthermore, bibliometric indicators are used for the quality and impact ranking of scientific journals (the case of the impact factor). In this review, alternative forms of web-based biomedical bibliometry are also mentioned, such as in particular the score of the Altmetric software, which is important for the assessment at the single article level, which is not ensured by the impact factor, and adopted by important biomedical journals. Ultimately, the criterion of adopting multiple metrics, both citational and non-citational, properly integrating them with each other, would result in an improved assessment of the quality and impact of the individual researcher, as well as biomedical journals.
301 Right endoventricular involvement in eosinophilic granulomatosis with polyangiitis and ventricular arrhythmia in a young patient with syncope
We report a case of a 30-year-old man, with previous hospitalizations for inflammatory sinusopa-thy and right parotid swelling, with evidence of increased LDH and hypereosinophilia. Due to right otalgia, headache, postural instability, a previous finding of left parietal subarachnoid hae-matoma and ischaemic hypodensities on CT brain scan; he was admitted to the hospital for sus-pected cerebritis (presence of proteins at lumbar puncture); consequently a diagnosis of vascular encephalopathy from probable primary cerebral vasculitis in the context of undetermined nature connectivity was made. This patient came to our attention complaining chest pain that had radiat-ed to the jugule, which lasted a few minutes, followed by a syncopal episode. Echocardiography showed a formation in the mid-apical portion of the right ventricle inflow tract. During hospitali-zation, clinicians, performing a CT-scan, excluded pulmonary embolism and expansive/infiltrative lesions; ECG showed negative T waves in D3, aVF, V3–V4 leads. Transesophageal echocardiography confirmed a right ventricle endocavitary mass, right ventricular diastolic dys-function and patent foramen ovale. Carotid artery Doppler showed a hypoechoic non-stenosing parietal apposition at the mid-proximal tract of the common carotid artery; on Doppler examina-tion, the common femoral vein showed a sleeve -like hypoechoic parietal apposition, and a prob-able right subclavian vein obstruction. MRI confirmed the presence of the mass in the right ven-tricle, as well as biventricular dysfunction and a delayed enhancement at the level of the left ven-tricular medioapical inferolateral wall and of the posterior papillary muscle. The main autoanti-body dosage, rheumatological and infectious disease markers were negative. During hospitaliza-tion, there was a single episode of self-limiting torsade de pointes. After evidence of fast growth of the RV mass it was suspected eosinophilic granulomatosis and patient underwent to biopsy that indicated thrombus with eosinophil infiltration. Therefore prednisone 25 mg and rivaroxaban 20 mg were started. After four months regression of mass on echocardiography was found. The Churg-Strauss syndrome, recently renamed eosinophilic granulomatosis with polyangiitis (EGPA) (in differential diagnosis with Loeffler's endocarditis) is a systemic necrotizing vasculitis with extravascular granulomas in eosinophilia. Cardiac involvement (in 15–60% of cases) can occur with myocarditis, heart failure, pericarditis, ar-rhythmias, coronary arteritis, valvulopathy and intracavitary thrombosis. In this specific case, the right ventricular mass), associated with ar-rhythmic episodes, can be related to the clinical manifestations that led to hospitalization.
484 Takotsubo syndrome and amyotrophic lateral sclerosis
Aims
Takotsubo syndrome (TTS) is a novel syndrome characterized by an acute, transient and reversible left ventricular regional systolic dysfunction, which resemble an acute myocardial infarction at presentation, but atherosclerotic obstruction of epicardial coronary arteries is not detected on angiography. It is triggered by important physical or psychological stressors, with women at post-menopause predominating and with multiple comorbidities, especially neurological ones. Amyotrophic Lateral Sclerosis (ALS) is the most common motor neuron disease and the progressive degeneration of motor neurons leads to their death, usually due to respiratory failure. An autopsy study remarked that heart failure represented the second most common cause of death. This study aimed to evaluate the relationship between TTS and SLA.
Methods and results
We have studied 85 patients admitted in our Coronary Care Unit, between September 2007 to June 2020, with a diagnosis of TTS according both to the Mayo Clinic criteria and the International Expert Consensus Document on TTS. Over the study period, the incidence of TTS increased from 2.5% in the first half of 2007 to 22.4% in 2019 and 9% in the first semester of 2020. We observed that the mean age at presentation was 70.3 ± 11.7, range 44–96, and 96.5% of the total patients (83/85) were over 50 years old; women constitute 85.8% of our cohort (73/85). We found various comorbidities: 9 (10.5%) had hypothyroidism secondary to Hashimoto's thyroiditis, 3 (3.5%) hyperthyroidism, 15 (17.6%) psychiatric disorders and 12 (14.1%) neurological diseases, of which 6 (7%) were ALS. On admission, patients with ALS had atypical symptoms (P = 0.003) and less frequently a typical chest pain (1 vs. 53, P = 0.038). The clinical conditions were more compromised, with greater impairment of overall systolic function (EF 35.3 ± 6.8 vs. 47 ± 10.4, P = 0.007) and severe systolic dysfunction present in 50% of patients, P = 0.035. During hospitalization ALS patients had a more complicated course: two (33%) patients presented cardiogenic shock, compared to only 3/79 (3.7%) patients not affected by ALS (P = 0.003) and ALS patients were treated more frequently with intravenous cathecolamines infusion (P = 0.001). Moreover, ALS patients had a higher incidence of acute respiratory failure and therefore underwent assisted ventilation more often than the other group (2/6, 33% vs. 4/79, 5%, P = 0.009). But we did not find a higher in-hospital mortality rate between the two groups (0% vs. 1.2%, P = 0.78).
Conclusion
Our study shows a high prevalence of ALS in patients with TS suggesting that ALS could be a predisposing condition to TTS, and even more so if associated to precipitating factors both emotional and physical, such as surgery, respiratory distress or infection. These data make us reflect on the need to search carefully for any acute cardiac dysfunction in patients suffering from ALS who manifest sudden worsening of clinical conditions as acute respiratory failure and thoracic discomfort, which may be an expression of TTS and require specific acute therapeutic support.
108 Prognostic impact of antiplatelet therapy in Takotsubo syndrome: a systematic review and meta-analysis of the literature
Aims
Over the past decades the association between single/double antiplatelet therapy use and outcome in Takotsubo Syndrome (TTS) has been widely investigated. While the most recent evidence seems to suggest a lack of benefit, antithrombotic therapy is still extensively prescribed in patients with stress cardiomyopathy.
Methods and results
To determine whether patients with TTS benefit from aspirin and/or other forms of antiplatelet therapy in terms of either short-term or long-term outcomes (death, myocardial infarction, TTS recurrence, stroke).
A Systematic Review with Meta-analysis was conducted. A comprehensive search of the literature included MEDLINE, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, EU Clinical Trial Register, References and contact with the authors. Methodological quality assessment and data extraction were completed in a systematic way. The review adhered to the PRISMA framework guidelines.
A total of 79 citations were identified, of which six studies were eligible for inclusion, for a total 1997 patients. Only one of them considered both short-term and long-term outcome. One reported only major cardiovascular (and cerebrovascular) events during the index event, while the remaining four focused only on long-term potential benefits. They were all retrospective cohort studies. The two only studies analysing the short-term prognostic role of antithrombotic drugs showed no consensus, also due to different Follow-up duration. Conversely, based on our data, the long-term use of single or dual antiplatelet therapy led to a significant higher incidence of the composite outcome (OR: 1.54; 95% CI 1.09–2.17; P = 0.014) and overall mortality (OR 1.72; 95% CI 1.07–2.77; P = 0.027). No other statistically significant results emerged.
Conclusion
The antiplatelet therapy administered after a diagnosis of Takotsubo syndrome had no benefit in improving the long-term outcomes and it may be even detrimental. The study showed conflicting results with regard to the short-term outcomes. The results of the present study should further promote the evaluation of the real impact of aspirin on outcome of Takotsubo patients. Future research on this topic, and in particular the design of adequately powered randomized controlled trials is warranted.
