Beyond the Cardiovascular Effects of Glucagon-like Peptide-1 Receptor Agonists: Body Slimming and Plaque Stabilization. Are New Statins Born?

Atherosclerosis is a chronic inflammatory disease characterized by lipid and inflammatory cell deposits in the inner layer of large- and medium-sized elastic and muscular arteries. Diabetes mellitus (DM) significantly increases the risk of cardiovascular diseases and the overall and cardiovascular mortality, and it is a pro-atherogenic factor that induces atherosclerosis development and/or accelerates its progression through a multifactorial process. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a new class of drugs, belonging to the armamentarium to fight type 2 DM, that have shown robust reductions in atherosclerotic events and all-cause mortality in all studies. Preclinical studies have shown that GLP-1RAs play a role in the immunomodulation of atherosclerosis, affecting multiple pathways involved in plaque development and progression. In this review, we wanted to explore the translational power of such preclinical studies by analyzing the most recent clinical trials investigating the atheroprotective effect of GLP-1RAs.

Gut Microbiota Composition and Cardiovascular Disease: A Potential New Therapeutic Target?

A great deal of evidence has revealed an important link between gut microbiota and the heart. In particular, the gut microbiota plays a key role in the onset of cardiovascular (CV) disease, including heart failure (HF). In HF, splanchnic hypoperfusion causes intestinal ischemia resulting in the translocation of bacteria and their metabolites into the blood circulation. Among these metabolites, the most important is Trimethylamine N-Oxide (TMAO), which is responsible, through various mechanisms, for pathological processes in different organs and tissues. In this review, we summarise the complex interaction between gut microbiota and CV disease, particularly with respect to HF, and the possible strategies for influencing its composition and function. Finally, we highlight the potential role of TMAO as a novel prognostic marker and a new therapeutic target for HF.

Effect of acute CORticosteroids on conduction defects after Transcatheter Aortic Valve Implantation: the CORTAVI study.

AIMS: Conduction abnormalities, requiring a permanent pacemaker (PPM), are the most common electrical complications after transcatheter aortic valve implantation (TAVI). The exact mechanism for conduction system defects is not yet clear. The local inflammatory process and edema are thought to play a role in the development of electrical disorders. Corticosteroids are effective anti-inflammatory and antiedematous agents. We aim to investigate the potential protective effect of corticosteroids on conduction defects after TAVI. METHODS: This is a retrospective study of a single center. We analyzed 96 patients treated with TAVI. Thirty-two patients received oral prednisone 50 mg for 5 days after the procedure. This population was compared with the control group. All patients were followed up after 2 years. RESULTS: Of the 96 patients included, 32 (34%) were exposed to glucocorticoids after TAVI. No differences in age, preexisting right bundle branch block or left bundle branch block, or valve type were seen among patients exposed to glucocorticoids versus those who were unexposed. We observed no significant differences between the two groups in the overall frequency of new PPM implantations during hospitalization (12% vs. 17%, P  = 0.76). The incidence of atrioventricular block (AVB) (STx 9% vs. non-STx 9%, P  = 0.89), right bundle branch block (STx 6% vs. non-STx 11%, P  = 0.71), and left bundle branch block (STx 34% vs. non-STx 31%, P  = 0.9) was not significantly different between the STx and non-STx groups. At 2 years after TAVI, none of the patients had implanted PPM or had severe arrhythmias documented by 24-h Holter ECG or cardiac examination. CONCLUSION: Oral prednisone treatment does not appear to significantly reduce the incidence of AVB requiring acute PPM implantation after TAVI.

Prevalence of Cardiovascular Risk Factors and Coronary Angiographic Findings in High-Risk Immigrant Communities in Italy.

BACKGROUND: The prevalence of coronary artery disease (CAD) considerably varies by ethnicity. High-risk populations include patients from Eastern Europe (EEP), the Middle East and North Africa (MENAP) and South Asia (SAP). METHODS: This retrospective study aims to highlight cardiovascular risk factors and specific coronary findings in high-risk immigrant groups. We examined the medical records and coronary angiographies of 220 patients from the above-mentioned high-risk ethnic groups referred for Acute Coronary Syndrome (ACS) and compared them with 90 Italian patients (IP) from 2016 to 2021. In the context of high-risk immigrant populations, this retrospective study aims to shed light on cardiovascular risk factors and particular coronary findings. We analyzed the medical records of 220 patients from the high-risk ethnic groups described above referred for ACS and compared them with 90 IPs between 2016 and 2021. In addition, we assessed coronary angiographies with a focus on the culprit lesion, mainly evaluating multi-vessel and left main disease. RESULTS: The mean age at the first event was 65.4 ± 10.2 years for IP, 49.8 ± 8.5 years for SAP (Relative Reduction (ReR) 30.7%), 51.9 ± 10.2 years for EEP (ReR 26%) and 56.7 ± 11.4 years for MENAP (ReR 15.3%); p < 0.0001. The IP group had a significantly higher prevalence of hypertension. EEP and MENAP had a lower prevalence of diabetes. EEP and MENAP had a higher prevalence of STEMI events; SAP showed a significant prevalence of left main artery disease (p = 0.026) and left anterior descending artery disease (p = 0.033) compared with other groups. In SAP, we detected a higher prevalence of three-vessel coronary artery disease in the age group 40-50. CONCLUSIONS: Our data suggest the existence of a potential coronary phenotype in several ethnicities, especially SAP, and understate the frequency of CV risk factors in other high-risk groups, supporting the role of a genetic influence in these communities.

Glucose variability: a new risk factor for cardiovascular disease.

AIMS AND DATA SYNTHESIS: Glucose variability (GV) is increasingly considered an additional index of glycemic control. Growing evidence indicates that GV is associated with diabetic vascular complications, thus being a relevant point to address in diabetes management. GV can be measured using various parameters, but to date, a gold standard has not been identified. This underscores the need for further studies in this field also to identify the optimal treatment. CONCLUSIONS: We reviewed the definition of GV, the pathogenetic mechanisms of atherosclerosis, and its relationship with diabetic complications.

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.

Treatment of HFpEF beyond the SGLT2-Is: Does the Addition of GLP-1 RA Improve Cardiometabolic Risk and Outcomes in Diabetic Patients?

Heart failure with preserved ejection fraction (HFpEF) is a common clinical syndrome frequently seen in elderly patients, the incidence of which is steadily increasing due to an ageing population and the increasing incidence of diseases, such as diabetes, hypertension, obesity, chronic renal failure, and so on. It is a multifactorial disease with different phenotypic aspects that share left ventricular diastolic dysfunction, and is the cause of about 50% of hospitalizations for heart failure in the Western world. Due to the complexity of the disease, no specific therapies have been identified for a long time. Sodium-Glucose Co-Transporter 2 Inhibitors (SGLT2-Is) and Glucagon-Like Peptide Receptor Agonists (GLP-1 RAs) are antidiabetic drugs that have been shown to positively affect heart and kidney diseases. For SGLT2-Is, there are precise data on their potential benefits in heart failure with reduced ejection fraction (HFrEF) as well as in HFpEF; however, insufficient evidence is available for GLP-1 RAs. This review addresses the current knowledge on the cardiac effects and potential benefits of combined therapy with SGLT2-Is and GLP-1RAs in patients with HFpEF.

Biomolecular Mechanisms of Cardiorenal Protection with Sodium-Glucose Co-Transporter 2 Inhibitors.

Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia and associated with an increased risk of morbidity and mortality, primarily from cardiovascular and renal diseases. Sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) are novel drugs for the treatment of type 2 DM and heart failure (HF). SGLT2-Is mediate protective effects on both the renal and cardiovascular systems. This review addresses the current knowledge on the biomolecular mechanisms of the cardiorenal protective effects of SGLT2-Is, which appear to act mainly through non-glucose-mediated pathways. Cardiorenal protection mechanisms lead to reduced chronic renal disease progression and improved myocardial and coronary endothelial function. Concomitantly, it is possible to observe reflected changes in biomarkers linked with diabetic kidney disease and HF.

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.

An unusual case of iatrogenic Twiddler's syndrome.

: Twiddler's syndrome is an uncommon cause of cardiac implantable electronic device malfunction, usually due to manipulation of the pulse generator. A few spontaneous cases have already been described. We present the unique case of a 77-year-old woman who experienced iatrogenic Twiddler's syndrome.

Safety of transvenous lead extraction according to centre volume: a systematic review and meta-analysis.

BACKGROUND: Transvenous lead extraction (TLE) is a complex invasive procedure and the experience of the operator and the team is a major determinant of procedural outcomes. AIM: Because of very limited data available on minimum procedural volumes to enable training and ongoing competency for TLEs, we performed a meta-analysis aimed at assessing the outcomes of TLE in the centres with low, medium, and high volume of procedures. METHODS: Of the 280 papers initially retrieved until February 2013, 66 observational studies met inclusion criteria and were included in at least one stratified meta-analysis: 17 were prospective studies; 47 had a retrospective design; and 2 were defined 'experience studies'. We included only articles published after the introduction of laser technique (year 1999). We divided the studies in low, medium, and high volume centres utilizing either the European Heart Rhythm Association (EHRA) or Lexicon classification criteria. RESULTS: When meta-analyses were carried out separately for the studies with larger and smaller sample sizes, either using EHRA or Lexicon classification criteria, no clear differences emerged in the combined rate of major complications or intraoperative deaths. In contrast, both minor complications and mortality at 30 days decreased as centre volume increased. CONCLUSIONS: In our meta-analysis of observational studies, patients who have been treated in higher volume centres have a lower probability of minor complications and death at 30 days regardless of the infection rate, length of lead duration, type of device, and type of extraction.

Prognostic role of heart rate variability in patients with ST-segment elevation acute myocardial infarction treated by primary angioplasty.

OBJECTIVES: The aim of our study was to assess the prognostic value of heart rate variability (HRV) in ST-segment elevation acute myocardial infarction (STEMI) patients treated by percutaneous transluminal coronary angioplasty (PTCA) and optimal medical therapy. METHODS: We enrolled 182 consecutive patients with a first STEMI (59.1 ± 11 years; 82.4% men) treated by primary PTCA. HRV was assessed on 24-hour Holter ECG recordings before discharge and 1 and 6 months after discharge. The primary end point was the occurrence of major clinical events (MCE), defined as death or new acute myocardial infarction (AMI). RESULTS: At a follow-up of 42 ± 23 months, MCE occurred in 14 patients (7.6%; 3 deaths and 11 re-AMIs). HRV parameters before discharge were significantly lower in patients with MCE, with standard deviation of all RR intervals (SDNN) and very low frequency and low frequency (LF) amplitude being the most predictive variables. HRV assessed at follow-up instead did not significantly predict MCE. At multivariate analysis, only SDNN (HR 0.97; p = 0.02) and LF (HR 0.90; p = 0.04) remained significantly associated with MCE. Lower tertile SDNN and LF values were associated with a multivariate HR of 3.91 (p = 0.015) and of 2.92 (p = 0.048), respectively. Similar results were observed considering re-AMI only as the end point. CONCLUSIONS: In STEMI patients treated by PTCA, HRV assessed before discharge was an independent predictor of MCE and re-AMI.

Effect of spinal cord stimulation in patients with refractory angina: evidence from observational studies.

OBJECTIVES: To review the evidence in observational studies of the effect of spinal cord stimulation (SCS) in patients with refractory angina pectoris (RAP) due to obstructive coronary artery disease. The effect of SCS in patients with refractory microvascular angina (MVA) also was assessed. MATERIALS AND METHODS: We reviewed the observational studies, published from 1987 to 2010, which investigated the effects of SCS on RAP. The number of angina attacks and that of taken nitrate tablets, as well as the class of angina, were considered as main outcome variables. The occurrence of adverse events related to the treatment also was assessed. RESULTS: The results showed a consistent reduction of the number of angina attacks (by 45-84%) and of consumption of short-acting nitrate tablets (by -75% to -94%), whereas the New York Heart Association and Canadian Cardiovascular Society class of angina were significantly improved in some studies. No case fatalities related to the therapy were reported. Significant clinical benefits were observed in some studies in patients with refractory MVA. Device-related infections and catheter dislodgment were the most significant and frequent side-effects, respectively. CONCLUSIONS: In observational studies, SCS showed to be an effective form of treatment for RAP, including refractory MVA. The treatment appears to be safe both at short- and long-term follow-up.

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.

Relationship between cardiac autonomic function and sustained ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillators.

AIMS: Low left ventricular ejection fraction (LVEF) is the main indication of implantable cardioverter defibrillators (ICD) in patients with dilated cardiomyopathy (DCM) for the primary prevention of sudden cardiac death, but ICD therapy at follow-up occurs in a minority of patients. We investigated whether heart rate variability (HRV) may improve risk stratification in DCM patients. METHODS AND RESULTS: We studied 42 patients (age 67.3 ± 3.5; 37 males) who had undergone ICD implant for either idiopathic or ischaemic DCM (LVEF <40%) 34.6 ± 19.7 months prior to the study (range 6-84). Patients underwent 24 h electrocardiographic Holter monitoring, and HRV was assessed over 2 hours in the afternoon showing stable sinus rhythm. Left ventricular ejection fraction was measured by two-dimensional echocardiography. The serum levels of C-reactive protein and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were also obtained. The primary endpoint was the occurrence of appropriate ICD shocks in the 6 months preceding the study. The occurrence of appropriate ICD discharge from ICD implant was considered as a secondary endpoint. In the last 6 months, appropriate ICD shocks had occurred in seven patients (17%). There were no differences between patients with and without ICD shocks in clinical variables, as well as in LVEF and in C-reactive protein and NT-proBNP serum levels. In contrast, most HRV parameters were significantly depressed in patients with, compared with those without, ICD shocks; the most significant difference was shown for the average of the standard deviations of RR intervals in all consecutive 5 min segments (n » 12) within the 2 h (26.7 ± 9 vs. 39.7 ± 14 ms; P = 0.02) in the time domain and for LF amplitude (8.4 ± 3 vs. 14.8 ± 7 ms; P = 0.02) in the frequency domain. Implantable cardioverter defibrillator discharge had occurred in 11 patients (26%) since ICD implant (average 35 months). No clinical or laboratory variable showed significant differences between patients with or without ICD discharge, except very low-frequency (VLF) amplitude (23.8 ± 7 vs. 30.8 ± 10.6 ms, respectively; P = 0.049). CONCLUSION: In ICD patients with reduced LVEF, several depressed HRV indices were significantly associated with appropriate ICD shocks in the previous 6 months, and VLF amplitude was the only variable significantly associated with ICD shocks recorded since ICD implant. These data suggest that full HRV analysis might be helpful for improving risk stratification for life-threatening ventricular arrhythmias and ICD indication in patients with DCM.

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.

Cardiac adrenergic nerve function in patients with cardiac syndrome X.

BACKGROUND: We previously found a severe impairment of cardiac uptake of I-metaiodobenzylguanidine (MIBG), an analogue of norepinephrine, on myocardial scintigraphy in a small group of patients with cardiac syndrome X (CSX), suggesting a dysfunction of cardiac adrenergic nerve fibres. In this study, we assessed the consistency of these previous findings in a larger group of these patients. METHODS: Planar and single-photon emission computed tomography MIBG myocardial scintigraphy was performed in 40 CSX patients (58 +/- 7 years, 17 men). Cardiac MIBG uptake was measured by the heart/mediastinum ratio and by a single-photon emission computed tomography regional cardiac MIBG uptake defect score (higher values = lower uptake). As a control group, we studied 20 healthy individuals (56 +/- 6 years, nine men). An exercise stress Tc-SestaMIBI myocardial scintigraphy was performed in 34 CSX patients (85%). RESULTS: Cardiac MIBG defects were observed in 30 patients (75%), with nine (22.5%) showing no cardiac MIBG uptake at all. Compared with controls, CSX patients showed a significantly lower heart/mediastinum ratio (1.70 +/- 0.35 vs. 2.1 +/- 0.22, P < 0.001) and a higher cardiac MIBG defect score (27 +/- 25 vs. 4.4 +/- 2.5, P < 0.001). No differences were found in lung MIBG uptake between the two groups. Reversible perfusion defects on stress myocardial scintigraphy were found in 17 out of 34 CSX patients (50%), all of whom also had abnormal cardiac MIBG uptake; cardiac MIBG uptake abnormalities were also present in nine of 17 patients with normal perfusion scintigraphic images. Cardiac MIBG uptake findings were similar in our first 12 patients and in the 28 patients studied subsequently. CONCLUSION: Our data show a relevant impairment of cardiac MIBG uptake in patients with CSX, suggesting that functional abnormalities in cardiac adrenergic nerve function may play a significant role in the mechanisms responsible for the syndrome.