Mortality after transvenous lead extraction: A risk prediction model for sustainable care delivery.

BACKGROUND AND AIMS: Transvenous lead extraction (TLE) has become a pivotal part of a comprehensive lead management strategy, dealing with a continuously increasing demand. Nonetheless, the literature about the long-term impact of TLE on survivals is still lacking. Given these knowledge gaps, the aim of our study was to analyse very long-term mortality in patients undergoing TLE in public health perspective. METHODS: This prospective, single-centre, observational study enrolled consecutive patients with cardiac implantable electronic device (CIED) who underwent TLE, from January 2005 to January 2021. The main goal was to establish the independent predictors of very long-term mortality after TLE. We also aimed at assessing procedural and hospitalization-related costs. RESULTS: We enrolled 435 patients (mean age 70 ± 12 years, with mean lead dwelling time 6.8 ± 16.7 years), with prevalent infective indication to TLE (92%). Initial success of TLE was achieved in 98% of population. After a median follow-up of 4.5 years (range: 1 month-15.5 years), 150 of the 435 enrolled patients (34%) died. At multivariate analysis, death was predicted by: age (≥77 years, OR: 2.55, CI: 1.8-3.6, p < 0.001), chronic kidney disease (CKD) defined as severe reduction of estimated glomerular filtration rate (eGFR <30 mL/min/1.73 m2 , OR: 1.75, CI: 1.24-2.4, p = 0.001) and systolic dysfunction assessed before TLE defined as left ventricular ejection fraction (LVEF) <40%, OR: 1.78, CI 1.26-2.5, p = 0.001. Mean extraction cost was €5011 per patient without reimplantation and €6336 per patient with reimplantation respectively. CONCLUSIONS: Our study identified three predictors of long-term mortality in a high-risk cohort of patients with a cardiac device infection, undergoing successful TLE. The future development of a mortality risk score before might impact on public health strategy.

PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection.

BACKGROUND: The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response. OBJECTIVES: The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19. METHODS: In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline. RESULTS: Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: -30%; 95% CI: -53.40% to -6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: -56% vs -21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: -37.50%; 95% CI: -68.20% to -6.70%). CONCLUSIONS: PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105).

Short-Term Atrioventricular Dysfunction Recovery after Post-TAVI Pacemaker Implantation.

Permanent pacemaker implantation (PPI) represents a frequent complication after transcatheter aortic valve implantation (TAVI) due to atrio-ventricular (AV) node injury. Predictors of early AV function recovery were investigated. We analyzed 50 consecutive patients (82 ± 6 years, 58% males, EuroSCORE: 7.8 ± 3.3%, STS mortality score: 5 ± 2.8%). Pacemaker interrogations within 4−6 weeks from PPI were performed to collect data on AV conduction. The most common indication of PPI was persistent third-degree (44%)/high-degree (20%) AV block/atrial fibrillation (AF) with slow ventricular conduction (16%) after TAVI. At follow-up, 13 patients (26%) recovered AV conduction (i.e., sinus rhythm with stable 1:1 AV conduction/AF with a mean ventricular response >50 bpm, associated with a long-term ventricular pacing percentage < 5%). At multivariate analysis, complete atrio-ventricular block independently predicted pacemaker dependency at follow-up (p = 0.019). Patients with persistent AV dysfunction showed a significant AV conduction time prolongation after TAVI (PR interval from 207 ± 50 to 230 ± 51, p = 0.02; QRS interval from 124 ± 23 to 147 ± 16, p < 0.01) compared to patients with recovery, in whom AV conduction parameters remained unchanged. Several patients receiving PPI after TAVI have recovery of AV conduction within a few weeks. Longer observation periods prior to PPI might be justified, and algorithms to minimize ventricular pacing should be utilized whenever possible.

Clinical features and outcomes of patients with stable or unstable chest pain and no-obstructive coronary artery disease.

Background: Coronary microvascular dysfunction can be responsible for both stable angina and acute coronary syndrome (ACS). There are scarce data, however, about comparisons of clinical characteristics and outcomes of these 2 groups of patients. Materials and methods: We studied 47 consecutive patients who underwent coronary angiography for angina syndromes and showed no obstructive stenosis. Patients were divided in 2 groups, according to their clinical presentation, i.e., stable angina (n = 21) or non-ST segment elevation ACS (NSTE-ACS; n = 26). An intracoronary acetylcholine (Ach) test was performed in 12 and 17 patients of the 2 groups, respectively. Angina status, assessed by Seattle Angina Questionnaire (SAQ), and clinical events were assessed after 1, 6, and 30 months. An exercise stress test was performed 1 month after discharge. Results: Clinical characteristics and exercise test results of the 2 groups were largely similar. Ach testing induced epicardial or microvascular spasm in 6 (50.0%) and 10 (58.8%) stable and NSTE-ACS patients, respectively (p = 0.72). Stable patients reported higher rates of angina, compared to NSTE-ACS patients, both at 1 (p = 0.04) and 30 months (81 vs. 50%, p = 0.036) of follow-up. SAQ scores were also lower in stable vs. NSTE-ACS patients. Ach testing results showed no association with clinical outcomes. Conclusion: Clinical characteristics and exercise and Ach testing results are similar in angina patients with no-obstructive coronary artery disease with a stable or NSTE-ACS presentation. Stable patients show a worse symptomatic outcome irrespective of Ach test results.

Atrioventricular conduction in PM recipients after transcatheter aortic valve implantation: Implications using Wenckebach point measurement.

Background: Atrioventricular (AV) conduction disturbances requiring permanent pacemaker implantation (PPI) are a common complication after transcatheter aortic valve implantation (TAVI). However, a significant proportion of patients might recover AV conduction at follow-up. Objectives: The aim of our study was to evaluate the recovery of AV conduction by determination through Wenckebach point in patients with PPI and therefore identify patients who could benefit from device reprogramming to avoid unnecessary RV pacing. Methods: We enrolled 43 patients that underwent PM implantation after TAVI at our Department from January 2018 to January 2021. PM interrogation was performed at follow-up and patients with native spontaneous rhythm were further assessed for AV conduction through WP determination. Results: A total of 43 patients requiring a PM represented the final study population, divided in patients with severely impaired AV conduction (no spontaneous valid rhythm or WP < 100; 26) and patients with valid AV conduction (WP ≥ 100; 17). In the first group patients had a significantly higher number of intraprocedural atrioventricular block (AVB) (20 vs. 1, p < 0.005), showed a significant higher implantation depth in LVOT (7.7 ± 2.2 vs. 4.4 ± 1.1, p < 0.05) and lower ΔMSID (-0.28 ± 3 vs. -3.94 ± 2, p < 0.05). Conclusion: AV conduction may recover in a significant proportion of patients. In our study, valve implantation depth in the LVOT and intraprocedural AV block are associated with severely impaired AV conduction. Regular PM interrogation and reprogramming are required to avoid unnecessary permanent right ventricular stimulation in patients with AV conduction recovery.

Coronary microvascular dysfunction and findings of heart failure with preserved ejection fraction in patients with microvascular angina.

BACKGROUND: Coronary microvascular dysfunction (CMD) may cause symptoms of myocardial ischemia (microvascular angina [MVA]), but recent studies suggested that it might also contribute to the syndrome of heart failure with preserved ejection fraction (HFpEF). In this study we assessed the relation of CMD with findings of HFpEF in MVA patients. METHODS: We enrolled 36 consecutive patients with MVA, in whom we assessed: 1) coronary blood flow (CBF) response to adenosine and cold pressor test (CPT) by color-Doppler echocardiography of the left anterior descending coronary artery; 2) complete echocardiographic examination; 3) N-terminal-pro-B-natriuretic peptide (NT-proBNP); 4) grade of dyspnea by the modified Medical Research Scale. RESULTS: Among patients, 15 had definite HFpEF findings (group 1), 12 had equivocal HFpEF findings (group 2) and 9 had no evidence of HFpEF findings (group 3). Group 1 patients were older, had more cardiovascular risk factors and higher NT-proBNP levels (P=0.018), and showed a higher prevalence of diastolic dysfunction. Left ventricle dimensions and systolic function, however, did not differ among groups. Dyspnea was also not significantly different among groups (P=0.19). CBF to adenosine was 1.85±0.47, 1.78±0.40 1.49±0.32 in group 1, 2 and 3, respectively (P=0.13). Similarly, CBF response to CPT was 1.57±0.4, 1.49±0.2 and 1.45±0.3 in the 3 groups, respectively (P=0.74). Both CBF response to adenosine and CPT showed no relation with the severity of dyspnea symptoms. CONCLUSIONS: Our data suggest that in patients with MVA there is no relation between the grade of impairment of coronary microvascular dilatation and findings of HFpEF.

Relation of endothelial and cardiac autonomic function with left ventricle diastolic function in patients with type 2 diabetes mellitus.

BACKGROUND AND AIMS: Diabetes mellitus (DM) is a risk factor for left ventricle (LV) diastolic dysfunction. Aim of this study was to investigate whether endothelial and/or autonomic dysfunction are associated with LV diastolic dysfunction in DM patients. METHODS: We studied 84 non-insulin-dependent type 2 DM (T2DM) patients with no heart disease by assessing: 1) LV diastolic function by echocardiography; 2) peripheral vasodilator function, by measuring flow-mediated dilation (FMD) and nitrate-mediate dilation (NMD); 3) heart rate variability (HRV) on 24-h Holter electrocardiographic monitoring. RESULTS: Twenty-five patients (29.8%) had normal LV diastolic function, while 47 (55.9%) and 12 (14.3%) showed a mild and moderate/severe diastolic dysfunction, respectively. FMD in these 3 groups was 5.25 ± 2.0, 4.95 ± 1.6 and 4.43 ± 1.8% (p = 0.42), whereas NMD was 10.8 ± 2.3, 8.98 ± 3.0 and 8.82 ± 3.2%, respectively (p = 0.02). HRV variables did not differ among groups. However, the triangular index tended to be lower in patients with moderate/severe diastolic dysfunction (p = 0.09) and a significant correlation was found between the E/e' ratio and both the triangular index (r = -0.26; p = 0.022) and LF amplitude (r = -0.29; p = 0.011). CONCLUSIONS: In T2DM patients an impairment of endothelium-independent, but not endothelium-dependent, dilatation seems associated with LV diastolic dysfunction. The possible role of cardiac autonomic dysfunction in diastolic dysfunction deserves investigation in larger populations of patients.

Powered sheaths for lead extraction.

Transvenous lead extraction (TLE) has seen a rapid expansion in the past 20 years. The procedure has changed from early techniques involving simple manual traction that frequently proved themselves ineffective for chronically implanted leads, and carried significant periprocedural risks including death, to the availability of a wide range of more efficacious techniques and tools, providing the skilled extractor with a well-equipped armamentarium. The reduction in morbidity and mortality associated with these new extraction techniques has widened indications to TLE from prevalent use in life-threatening situations, such as infection and sepsis, to a more widespread use even in noninfectious situations such as malfunctioning leads. Powered sheaths have been a remarkable step forward in this improvement in TLE procedures and recent registries at high-volume centers report high success rates with exceedingly low complication rates. This review is aimed at describing technical features of powered sheaths as well as reported performance during TLE procedures.

Relation of vascular dilator function and cardiac autonomic function with coronary angiography findings in patients with non-ST segment elevation acute coronary syndrome.

BACKGROUND: A sizeable number of patients with a diagnosis of non-ST segment elevation acute coronary syndrome show non-obstructive coronary artery disease. In this study we assessed whether differences in vascular and cardiac autonomic function exist between non-ST segment elevation acute coronary syndrome patients with obstructive or non-obstructive coronary artery disease. METHODS AND RESULTS: Systemic endothelium-dependent and independent vascular dilator function (assessed by flow-mediated dilation and nitrate-mediated dilation of the brachial artery, respectively) and cardiac autonomic function (assessed by time-domain and frequency-domain heart rate variability parameters) were assessed on admission in 120 patients with a diagnosis of non-ST segment elevation acute coronary syndrome. Patients were divided into two groups according to coronary angiography findings: (a) 59 (49.2%) with obstructive coronary artery disease (≥50% stenosis in any epicardial arteries); (b) 61 (50.8%) with non-obstructive coronary artery disease. No significant differences between the two groups were found in both flow-mediated dilation (5.03 ± 2.6 vs. 5.40 ± 2.5%, respectively; P = 0.37) and nitrate-mediated dilatation (6.79 ± 2.8 vs. 7.30 ± 3.4%, respectively; P = 0.37). No significant differences were also observed between the two groups both in time-domain and frequency-domain heart rate variability variables, although the triangular index tended to be lower in obstructive coronary artery disease patients (30.2 ± 9.5 vs. 33.9 ± 11.6, respectively; P = 0.058). Neither vascular nor heart rate variability variables predicted the recurrence of angina, requiring emergency room admission or re-hospitalisation, during 11.3 months of follow-up. CONCLUSIONS: Among patients admitted with a diagnosis of non-ST segment elevation acute coronary syndrome we found no significant differences in systemic vascular dilator function and cardiac autonomic function between those with obstructive coronary artery disease and those with non-obstructive coronary artery disease.

Relation of vascular dilator function and cardiac autonomic function with coronary angiography findings in patients with non-ST segment elevation acute coronary syndrome.

BACKGROUND: A sizeable number of patients with a diagnosis of non-ST segment elevation acute coronary syndrome show non-obstructive coronary artery disease. In this study we assessed whether differences in vascular and cardiac autonomic function exist between non-ST segment elevation acute coronary syndrome patients with obstructive or non-obstructive coronary artery disease. METHODS AND RESULTS: Systemic endothelium-dependent and independent vascular dilator function (assessed by flow-mediated dilation and nitrate-mediated dilation of the brachial artery, respectively) and cardiac autonomic function (assessed by time-domain and frequency-domain heart rate variability parameters) were assessed on admission in 120 patients with a diagnosis of non-ST segment elevation acute coronary syndrome. Patients were divided into two groups according to coronary angiography findings: (a) 59 (49.2%) with obstructive coronary artery disease (≥50% stenosis in any epicardial arteries); (b) 61 (50.8%) with non-obstructive coronary artery disease. No significant differences between the two groups were found in both flow-mediated dilation (5.03 ± 2.6 vs. 5.40 ± 2.5%, respectively; P = 0.37) and nitrate-mediated dilatation (6.79 ± 2.8 vs. 7.30 ± 3.4%, respectively; P = 0.37). No significant differences were also observed between the two groups both in time-domain and frequency-domain heart rate variability variables, although the triangular index tended to be lower in obstructive coronary artery disease patients (30.2 ± 9.5 vs. 33.9 ± 11.6, respectively; P = 0.058). Neither vascular nor heart rate variability variables predicted the recurrence of angina, requiring emergency room admission or re-hospitalisation, during 11.3 months of follow-up. CONCLUSIONS: Among patients admitted with a diagnosis of non-ST segment elevation acute coronary syndrome we found no significant differences in systemic vascular dilator function and cardiac autonomic function between those with obstructive coronary artery disease and those with non-obstructive coronary artery disease.

Sex-Specific Cut-Offs for High-Sensitivity Cardiac Troponin: Is Less More?

Management of patients presenting to the Emergency Department with chest pain is continuously evolving. In the setting of acute coronary syndrome, the availability of high-sensitivity cardiac troponin assays (hs-cTn) has allowed for the development of algorithms aimed at rapidly assessing the risk of an ongoing myocardial infarction. However, concerns were raised about the massive application of such a simplified approach to heterogeneous real-world populations. As a result, there is a potential risk of underdiagnosis in several clusters of patients, including women, for whom a lower threshold for hs-cTn was suggested to be more appropriate. Implementation in clinical practice of sex-tailored cut-off values for hs-cTn represents a hot topic due to the need to reduce inequality and improve diagnostic performance in females. The aim of this review is to summarize current evidence on sex-specific cut-off values of hs-cTn and their application and usefulness in clinical practice. We also offer an extensive overview of thresholds reported in literature and of the mechanisms underlying such differences among sexes, suggesting possible explanations about debated issues.

Gender related differences in treatment and response to statins in primary and secondary cardiovascular prevention: The never-ending debate.

Statins are a main curbstone in the prevention of cardiovascular disease (CVD), pandemic in 21st century. CVD displays evident sex and gender differences, not only in clinical manifestation and outcomes but also in pharmacological treatment. Whether statin therapy should be differentially prescribed according to sex is a matter of debate. Aside a different pharmacological action, statins are not proven to be less effective in one gender comparing to the other, nor to be less safe. Nevertheless, up to date evidence shows that statins have not been adequately tested in women, especially in primary prevention trials. Since data-lacking, making a treatment decision on women is potentially harmful, although female individuals represent the majority of the population and they have a greater lifetime CVD risk. Therefore, adequately powered randomized control trials with longer follow-up are warranted to establish if a benefit on CV events and mortality prevention exists in both sexes. The aim of the present review is to summarize the sex and gender differences in statin use: it raises concerns and updates perspectives towards an evidence-based and sex-tailored prevention of CVD management.

Impaired flow-mediated dilation in hospitalized patients with community-acquired pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is complicated by cardiovascular events as myocardial infarction and stroke but the underlying mechanism is still unclear. We hypothesized that endothelial dysfunction may be implicated and that endotoxemia may have a role. METHODS: Fifty patients with CAP and 50 controls were enrolled. At admission and at discharge, flow-mediated dilation (FMD), serum levels of endotoxins and oxidative stress, as assessed by serum levels of nitrite/nitrate (NOx) and isoprostanes, were studied. RESULTS: At admission, a significant difference between patients with CAP and controls was observed for FMD (2.1±0.3 vs 4.0±0.3%, p<0.001), serum endotoxins (157.8±7.6 vs 33.1±4.8pg/ml), serum isoprostanes (341±14 vs 286±10 pM, p=0.009) and NOx (24.3±1.1 vs 29.7±2.2µM). Simple linear correlation analysis showed that serum endotoxins significantly correlated with Pneumonia Severity Index score (Rs=0.386, p=0.006). Compared to baseline, at discharge CAP patients showed a significant increase of FMD and NOx (from 2.1±0.3 to 4.6±0.4%, p<0.001 and from 24.3±1.1 to 31.1±1.5µM, p<0.001, respectively) and a significant decrease of serum endotoxins and isoprostanes (from 157.8±7.6 to 55.5±2.3pg/ml, p<0.001, and from 341±14 to 312±14 pM, p<0.001, respectively). Conversely, no changes for FMD, NOx, serum endotoxins and isoprostanes were observed in controls between baseline and discharge. Changes of FMD significantly correlated with changes of serum endotoxins (Rs=-0.315; p=0.001). CONCLUSIONS: The study provides the first evidence that CAP is characterized by impaired FMD with a mechanism potentially involving endotoxin production and oxidative stress.