Long-term follow-up of heart transplant patients treated with permanent pacemaker: a monocentric study

Abstract Funding Acknowledgements Type of funding sources: None. Background and purpose Permanent pacemaker implantation (PPMi) is needed in about 5% of patients following heart transplant (HTx) primarily due to sinus node dysfunction (SND), which commonly occurs in an early phase, or to atrio-ventricular block (ABV), which is common later on. Currently, data on rate of ventricular pacing (VP) is lacking and little is known on long-term outcomes after PPMi. Methods This was a retrospective, monocentric study. Among 1123 patients treated with HTx, all with biatrial technique, from november 1985 to march 2019 at our institution, 61 (5.4%) patients needed PPMi. PM parameters, clinical and echocardiographic data were collected at 1 month and at 1-3-5-10 years follow-up. The primary aim was to analyse the percentage of right ventricular pacing in the overall population and in subgroups stratified by the timing of PPMi and by pacing indication. Secondary endpoints were to analyze long-term outcomes according to the percentage of ventricular pacing and to the type of implanted PM (single vs. dual chamber). Results Among patients treated with PPMi (68.9% single-chamber), 62.2% were implanted for SND and 36% for AVB. Early PPMi (< 3 months after HTx), occurred in 34.4% of patients, mainly due to SND, while late PPMi (> 3 months after HTx) occurred in 65,6% with an equal distribution between SND and AVB. Median follow-up time from HTx was 140 months and 82 months from PPMi. Overall mean rate of VP was 21%. Rate of VP was higher in patients implanted early rather than late after HTx, both at 1 month (91% vs 2%, P = 0,002) and at 1 year after the procedure (43 vs 1, P = 0,037). Patients with AVB had a greater rate of VP compared to those implanted for SND, irrespective of timing of implantation and these findings were still present at 3 and 5 years follow-up (62 vs 1%, P = 0,011 at 3 years and 80 vs 6%, P = 0,002 at 5 years). VP declined progressively after PPM implantation. No differences were observed in terms of 10-years mortality between early vs late PPMi, dual vs single-chamber and mean VP > 21% vs ≤ 21%. Conclusions Patients treated with PPMi after HTx show on average low percentage of VP over long-term follow-up. AV block indication and early implantation are associated with a higher percentage of VP. The rate of VP, the timing of PPMi and the use of single vs dual chamber PM do not affect overall prognosis or left ventricular systolic function. Our data may justify implantation of a single-chamber PPM, which bears less complications and procedural time, in the majority of HTx patients needing PPMi

Barriers associated with emergency medical service activation in Italian patients with ST-segment elevation acute coronary syndromes

Abstract Background Many ST-segment elevation acute coronary syndrome (STEACS) patients fail to activate the Emergency Medical System (EMS), with possible dramatic consequences. Prior studies focusing on barriers to EMS activation include patients with any acute coronary syndrome (ACS) without representation of southern European populations. However, barriers are influenced by the ACS type and by socio-demographic and racial factors. Purpose We aimed to investigate the barriers to EMS call for patients diagnosed for STEACS in Italy. Methods A prospective, single-center, survey-based study, including all the patients treated with primary percutaneous coronary intervention for STEACS in a tertiary hospital in northern Italy from 1st June 2018 to 31st May 2020. Results The questionnaire was filled out by 293 patients. The majority of the participants were males (74%), married (70.4%), with a high-school degree (38.4%) and with a median age of 62 years. Chest pain as a possible symptom related to a cardiovascular attack is known by most of the respondents (89%), and left arm pain/shake by 53.7% of them, whilst the other possible signs and symptoms (i.e. dyspnea, asthenia, sweating, nausea, vomiting, dizziness) were unknown to the majority of the participants. Only 191 (65.2%) of the participants activated the EMS after symptoms onset. The main reasons for not calling EMS were the perception that symptoms were not related to an important health problem (45.5%) and that a private vehicle is faster than EMS to reach the hospital (34.7%). The median time to first medical contact was 60 minutes, and it was significantly higher in the patients who did not called EMS compared to those who did (180 [60–420] mins vs 35 [15–120] mins, p<0.001). The patients who called a private doctor after symptoms onset did not called EMS more frequently than those who did not (5.9% vs 8.2%, p=0.3). Moreover, 30% of the patients who did not call the EMS would still act in the same way if a new episode occurred and the main reasons for this were that they think to be faster than EMS (57.1%) and to live close to the hospital (17.9%). Analyzing predictors of EMS activation, only prior history of cardiovascular disease has been demonstrated to be a predictor of calling the EMS in case of symptoms suspected for STEACS. Conclusions Our study, from the southern Europe, showed that a substantial percentage of patients with symptoms suspected for STEACS preferred private vehicle rather than activating the EMS. Our results highlight the need for information campaigns targeted to both the general population and medical doctors, stressing that the EMS is faster than a private vehicle to direct the patient to the right hospital and increasing the awareness of the people on the type of possible heart attack symptoms, which seem to be the most neglected issues by patients who did not call the EMS. Funding Acknowledgement Type of funding sources: None

Anti-Human Tissue Factor Antibody Ameliorated Intestinal Ischemia Reperfusion-Induced Acute Lung Injury in Human Tissue Factor Knock-In Mice

BACKGROUND: Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS). Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: Human tissue factor knock-in (hTF-KI) transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859) were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v.) attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. CONCLUSIONS: This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies

How do cardiologists select patients for dual antiplatelet therapy continuation beyond 1 year after a myocardial infarction? Insights from the EYESHOT Post-MI Study

Background: Current guidelines suggest to consider dual antiplatelet therapy (DAPT) continuation for longer than 12 months in selected patients with myocardial infarction (MI). Hypothesis: We sought to assess the criteria used by cardiologists in daily practice to select patients with a history of MI eligible for DAPT continuation beyond 1 year. Methods: We analyzed data from the EYESHOT Post-MI, a prospective, observational, nationwide study aimed to evaluate the management of patients presenting to cardiologists 1 to 3 years from the last MI event. Results: Out of the 1633 post-MI patients enrolled in the study between March and December 2017, 557 (34.1%) were on DAPT at the time of enrolment, and 450 (27.6%) were prescribed DAPT after cardiologist assessment. At multivariate analyses, a percutaneous coronary intervention (PCI) with multiple stents and the presence of peripheral artery disease (PAD) resulted as independent predictors of DAPT continuation, while atrial fibrillation was the only independent predictor of DAPT interruption for patients both at the second and the third year from MI at enrolment and the time of discharge/end of the visit. Conclusions: Risk scores recommended by current guidelines for guiding decisions on DAPT duration are underused and misused in clinical practice. A PCI with multiple stents and a history of PAD resulted as the clinical variables more frequently associated with DAPT continuation beyond 1 year from the index MI

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D