Advances in Imaging for Tricuspid Transcatheter Edge-to-Edge Repair: Lessons Learned and Future Perspectives.

Severe tricuspid valve (TV) regurgitation (TR) has been associated with adverse long-term outcomes in several natural history studies, but isolated TV surgery presents high mortality and morbidity rates. Transcatheter tricuspid valve interventions (TTVI) therefore represent a promising field and may currently be considered in patients with severe secondary TR that have a prohibitive surgical risk. Tricuspid transcatheter edge-to-edge repair (T-TEER) represents one of the most frequently used TTVI options. Accurate imaging of the tricuspid valve (TV) apparatus is crucial for T-TEER preprocedural planning, in order to select the right candidates, and is also fundamental for intraprocedural guidance and post-procedural follow-up. Although transesophageal echocardiography represents the main imaging modality, we describe the utility and additional value of other imaging modalities such as cardiac CT and MRI, intracardiac echocardiography, fluoroscopy, and fusion imaging to assist T-TEER. Developments in the field of 3D printing, computational models, and artificial intelligence hold great promise in improving the assessment and management of patients with valvular heart disease.

Combined MitraClip and Left Atrial Appendage Occlusion: Is It Still a Utopia?

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting 32 million individuals worldwide, particularly the elderly. It is the main cause of ischemic strokes. Oral anticoagulation (OAC) is the gold standard strategy for stroke prevention. Still, there is a not negligible share of patients who have contraindications to this therapy, more frequently due to an increased risk of bleeding. AF is often associated with moderate-severe mitral regurgitation (MR), the second most frequent valvular disease in elderly patients. Data from the literature reported that more than half of patients with severe mitral regurgitation are not suitable candidates for cardiac surgery. Given the progressive aging of the population and the simultaneous increase in the number of patients with comorbidities, the advent of new therapeutic strategies, such as the combined approach of Left Atrial Appendage Occlusion (LAAO) and MitraClip procedure, is acquiring great interest. At present, the category of patients who may benefit from combined percutaneous therapies and the long-term risks and benefits might not have been identified. Despite the efforts of researchers, the correct selection of patients is a very important clinical need that has not yet been met to avoid committing human and financial resources to interventions that may be unnecessary. It is conceivable that the most modern and recent innovations in cardiovascular imaging, particularly three-dimensional echocardiography and new methods of volume imaging, could improve our ability to select patients appropriately. Since data in the literature are scarce, future studies will be needed to evaluate the efficacy and safety of combined MitraClip and LAA occlusion.

Platelet reactivity and endothelial function in children of patients with early acute myocardial infarction.

AIMS: To assess whether platelet reactivity is increased in offspring of patients with early acute myocardial infarction (AMI) and its possible relation with endothelial dysfunction. METHODS AND RESULTS: We studied 23 healthy children (15±3 years, 13 males) of patients with early AMI (≤50 years old; Group 1) and 21 healthy children of healthy subjects without any history of cardiovascular disease (14±3 years, 10 males; Group 2). Platelet reactivity was assessed by flow cytometry as the increase in monocyte-platelet aggregates (MPA) and CD41 and PAC-1 platelet expression in response to exercise stress test (EST), adenosine diphosphate (ADP) stimulation (10(-7) M), or both. Endothelial function was assessed by measuring brachial artery dilation during post-ischaemic forearm hyperaemia [flow-mediated dilation (FMD)]. Both EST and ADP induced a higher percentage increase in platelet receptor expression in Group 1, compared with Group 2, with the most significant difference being shown for the response to the combined stimuli (e.g. MPA, 23.1±12 vs. 5.63±8%, P<0.001; platelet PAC-1, 57.7±47 vs. 13.2±7%, P<0.001). Compared with Group 2, Group 1 children showed lower FMD (10.7±3.1 vs. 8.0±2.9%, respectively; P=0.007). However, no significant association was found between FMD and platelet reactivity. CONCLUSION: Our results show increased platelet reactivity in children of patients with early AMI; the finding was not significantly correlated with endothelial dysfunction, suggesting that other mechanisms are mainly involved in the enhanced platelet response to agonistic stimuli.

Evidence of increased platelet reactivity in the first six months after acute ST segment elevation myocardial infarction.

INTRODUCTION: Platelets play a crucial role in the pathogenesis of acute coronary syndromes. Accordingly, previous studies showed increased platelet reactivity on admission in these patients. In this study we assessed platelet reactivity at short-medium term follow-up in patients with ST-segment elevation acute myocardial infarction (STEMI). MATERIALS AND METHODS: Fifty-nine patients (58 ± 11 years, 45 men), treated with primary angioplasty, were studied 1 month after STEMI. Thirty-five patients were retested at 6 months. Twenty matched patients with stable coronary artery disease served as controls. Platelet reactivity was assessed by flow cyometry at rest and at peak exercise, with and without adenosine diphosphate (ADP) stimulation, by measuring monocyte-platelet aggregates (MPAs) and glycoprotein IIb/IIIa (CD41) expression in the MPA gate, and CD41 and fibrinogen receptor (PAC-1) expression in the platelet gate. RESULTS: Compared to controls, basal MPAs and CD41 in the MPA gate were higher in STEMI patients both at 1 month (p = 0.001 and p = 0.002, respectively) and at 6 months (p = 0.03 and p = 0.01, respectively). Basal CD41 and PAC-1 expression was also higher in STEMI patients at the two assessments compared to controls (P<0.001 for both). Exercise induced a similar increase in platelet reactivity in patients and controls. ADP induced a higher increase in CD41 platelet expression in STEMI patients compared to controls both at 1 and 6 months (P < 0.001). CONCLUSION: Platelet reactivity is increased in the first 6 months after STEMI. The persistence of increased platelet reactivity in this time period may play a role in the early recurrence of coronary events after STEMI.

Inflammation-related effects of adjuvant influenza A vaccination on platelet activation and cardiac autonomic function.

BACKGROUND: Inflammation, platelet reactivity and cardiac autonomic dysfunction increase the risk of cardiovascular events, but the relationships between these prognostic markers are poorly defined. In this study, we investigated the effect of an inflammatory stimulus (influenza A vaccine) on platelet activation and cardiac autonomic function. METHODS: We measured serum C-reactive protein (CRP) and interleukin-6 levels, monocyte-platelet aggregates (MPAs) and monocyte/platelet receptor expression before and after adjuvant influenza A vaccination in 28 patients with type II diabetes (mean age 62.1 ± 8 years, 18 men). Twenty-four-hour Holter electrocardiogram was recorded 24 h before and after vaccination; heart rate variability (HRV) was assessed as a measure of cardiac autonomic function. RESULTS: Inflammatory cytokines, MPA formation and monocyte/platelet receptor expression increased after vaccination. CRP was 2.6 ± 2.8 and 7.1 ± 5.7 mg L⁻¹ 48 h before and after vaccination, respectively (P < 0.0001). HRV parameters decreased after vaccination compared to baseline, with very low-frequency amplitude showing the most significant change (34.6 ± 11.8 and 31.0 ± 10.2 ms 48 h before and after vaccination, respectively; P = 0.002). A significant correlation was found between percentage changes in CRP levels and in most HRV variables, with the most significant correlations between changes in CRP levels and changes in standard deviation of all normal RR intervals (r = 0.43; P = 0.02). CONCLUSIONS: Together with an inflammatory reaction, influenza A vaccine induced platelet activation and sympathovagal imbalance towards adrenergic predominance. Significant correlations were found between CRP levels and HRV parameters, suggesting a pathophysiological link between inflammation and cardiac autonomic regulation. The vaccine-related platelet activation and cardiac autonomic dysfunction may transiently increase the risk of cardiovascular events.

Brief low-workload myocardial ischaemia induces protection against exercise-related increase of platelet reactivity in patients with coronary artery disease.

OBJECTIVE: In patients with acute myocardial infarction, pre-infarction angina is associated with smaller infarct size, probably mainly through myocardial protection induced by ischaemic preconditioning. However, in models of recurrent thrombosis myocardial ischaemia also improves arterial patency. This study investigated whether myocardial ischaemia has any effect on platelet function in patients with coronary artery disease. PATIENTS AND DESIGN: Twenty patients with low-workload myocardial ischaemia underwent, in a randomised crossover study, two treadmill exercise stress tests (EST) on two separate days: a single maximal EST (EST-1) and a maximal EST (EST-2) performed 45 minutes after a low-workload EST stopped at 1-mm ST depression (p-EST). Platelet reactivity was evaluated by measuring the closure time in response to ADP/collagen by the PFA-100 method, and monocyte-platelet aggregate (MPA) formation and CD41 platelet expression, with and without ADP stimulation, by flow cytometry. RESULTS: Compared to resting values, closure time decreased at peak EST-1 (p<0.001) but not at peak EST-2. MPA after ADP stimulation increased more significantly at peak EST-1 compared with peak EST-2 (p<0.001). Repetition in seven patients of the pEST/EST-2 protocol after intravenous administration of the adenosine antagonist theophylline showed prevention of the effects of p-EST on exercise-induced platelet reactivity. CONCLUSIONS: A short episode of myocardial ischaemia induces protection against an exercise-induced increase of platelet reactivity. These data also suggest a role for adenosine in this phenomenon.

Long-term prognosis of patients with cardiac syndrome X.

BACKGROUND: Previous follow-up studies of patients with cardiac syndrome X (CSX) reported good prognosis. However, some recent reports challenged this finding by showing appreciable mortality rates in patients with angina and normal coronary arteries admitted for acute coronary syndromes. METHODS: We performed clinical follow-up of 155 patients (mean age 58.9+/-10 years, 40 men) with typical CSX. The occurrence of major cardiac events (cardiac death, acute myocardial infarction), readmission for chest pain, revascularization procedures, angina status, and non cardiac events during follow-up were collected for each patient. RESULTS: At a mean follow-up time of 137+/-78 months (range 24-372) from the onset of symptoms, 4 patients died, 3 for cancers and 1 for acute pancreatitis. No patient died from cardiovascular causes or had any major cardiovascular event. Hospital readmission for recurrent chest pain was reported by 89 patients (58%), and 33 (22%) underwent at least one more coronary angiography. During follow-up, chest pain had remained unchanged in 33% of patients and had worsened in 14% of patients. CONCLUSION: Our data show that patients with CSX have excellent long-term clinical prognosis. A significant number of patients, however, shows persistence or worsening of symptoms, as well as further recurrence to medical evaluation.

Predictors of exercise-induced platelet reactivity in patients with chronic stable angina.

OBJECTIVE: Previous studies have shown that exercise increases platelet reactivity in patients with coronary artery disease (CAD). However, the response of platelet reactivity to exercise is considerably variable and its predictors are poorly known. METHODS: We studied 214 consecutive patients (age 61.9 +/- 9 years, 167 men) with stable angina and obstructive coronary artery disease. All patients underwent a symptom-limited treadmill exercise stress test. Venous blood samples were collected before and at peak exercise. Platelet reactivity was assessed by the platelet function analyzer system as the time for flowing whole blood to occlude a collagen-adenosine diphosphate ring (closure time: shorter times = higher reactivity). Both closure time at peak exercise and the exercise-induced change in closure time from rest were assessed as an expression of exercise-related platelet reactivity. RESULTS: Closure time decreased significantly with exercise in the whole population (from 95.9 +/- 22 to 81.2 +/- 18 s, P < 0.001). The only variable significantly associated with closure time at peak exercise was hematocrit (P = 0.003). Basal systolic blood pressure (P = 0.023) and lack of nitrate use (P = 0.03), on the contrary, were the only variables significantly associated with increased exercise-induced closure time change. Peak hematocrit maintained an independent association with peak closure time in multivariable analysis, although the correlation was mild. No variable, on the contrary, was associated with exercise-induced platelet reactivity after correction for basal closure time values at multivariable analyses. CONCLUSION: Among stable coronary artery disease patients, platelet reactivity after exercise cannot be reliably predicted by several common clinical and laboratory variables.

Effect of vagal nerve stimulation on systemic inflammation and cardiac autonomic function in patients with refractory epilepsy.

OBJECTIVE: Recent data suggest that vagus nerve stimulation (VNS) can inhibit cytokine release by inflammatory cells. Accordingly, an association between impaired cardiac parasympathetic function, as assessed by heart rate variability (HRV), and increased markers of inflammation has recently been reported. In this study we assessed the effect of direct left VNS on inflammatory markers and HRV in patients with refractory epilepsy. METHODS: A 24-hour electrocardiogram Holter recording was performed both at baseline and after 3 months of left VNS in 8 patients (age 32 +/- 24 years, 2 men) who underwent implantation of a VNS device because of refractory epilepsy. Tumor necrosis factor-alpha, interleukin-6 and C-reactive protein serum levels were measured, as markers of inflammation, at the same times. RESULTS: No significant changes were found after 3 months of left VNS, compared to baseline, both for HRV variables and inflammatory markers. Also, no consistent correlation could be demonstrated between HRV parameters and inflammatory markers in these patients. CONCLUSIONS: Our data in epileptic patients without cardiovascular disease failed to show a significant effect of left VNS on cardiac autonomic function and on systemic inflammation at short-term follow-up.