Takotsubo Syndrome and Gender Differences: Exploring Pathophysiological Mechanisms and Clinical Differences for a Personalized Approach in Patient Management.

Takotsubo syndrome (TTS), also known as the broken-heart syndrome, is a reversible condition typically observed in female patients presenting for acute coronary syndromes (ACS). Despite its increasing incidence, TTS often remains undiagnosed due to its overlap with ACS. The pathophysiology of TTS is complex and involves factors such as coronary vasospasm, microcirculatory dysfunction, increased catecholamine levels, and overactivity of the sympathetic nervous system. Diagnosing TTS requires a comprehensive approach, starting with clinical suspicion and progressing to both non-invasive and invasive multimodal tests guided by a specific diagnostic algorithm. Management of TTS should be personalized, considering potential complications, the presence or absence of coronary artery disease (CAD), diagnostic test results, and the patient's clinical course. The current data primarily derive from case series, retrospective analyses, prospective registries, and expert opinions. In recent years, there has been growing recognition of gender differences in the pathophysiology, presentation, and outcomes of TTS. This review provides an updated overview of gender disparities, highlighting the importance of tailored diagnostic and management strategies.

Aspirin in Primary Prevention: Looking for Those Who Enjoy It.

Based on a wealth of evidence, aspirin is one of the cornerstones of secondary prevention of cardiovascular disease. However, despite several studies showing efficacy also in primary prevention, an unopposed excess risk of bleeding leading to a very thin safety margin is evident in subjects without a clear acute cardiovascular event. Overall, the variability in recommendations from different scientific societies for aspirin use in primary prevention is a classic example of failure of simple risk stratification models based on competing risks (atherothrombosis vs. bleeding), perceived to be opposed but intertwined at the pathophysiological level. Notably, cardiovascular risk is dynamic in nature and cannot be accurately captured by scores, which do not always consider risk enhancers. Furthermore, the widespread use of other potent medications in primary prevention, such as lipid-lowering and anti-hypertensive drugs, might be reducing the benefit of aspirin in recent trials. Some authors, drawing from specific pathophysiological data, have suggested that specific subgroups might benefit more from aspirin. This includes patients with diabetes and those with obesity; sex-based differences are considered as well. Moreover, molecular analysis of platelet reactivity has been proposed. A beneficial effect of aspirin has also been demonstrated for the prevention of cancer, especially colorectal. This review explores evidence and controversies concerning the use of aspirin in primary prevention, considering new perspectives in order to provide a comprehensive individualized approach.

Usefulness of last generation insertable cardiac monitors in the diagnosis of unexplained syncope.

AIMS: Guidelines recommend insertable cardiac monitor (ICM) in the early phases of the evaluation of unexplained syncope (US) syncope, when an arrhythmic etiology is suspected. We examined the diagnostic yield of the last generation ICM (LG-ICM) to establish the causes of US, by assessing in the clinical practice the incidence of: relevant arrhythmia diagnosis, syncope recurrences and CM-guided cardiac electronic device (CIED) implantation. We investigated also baseline patient characteristics associated to an increased risk of relevant arrhythmias and of syncope recurrence. METHODS: Data prospectively collected from consecutive patients receiving LG-ICM for investigation of US or presyncope in our institution between November 2020 and January 2023 were analyzed. RESULTS: A total of 109 patients (mean age 64.4 ± 16.1 years, 40.4% women) with US or pre-syncope episodes underwent implantation of the LG-ICM. During a mean follow-up of 11.7 ± 8.1 months, LG-ICM diagnostic yield was 42%. In particular, LG-ICM detected cardiac arrhythmias in 29 (27%) patients (in 6 out of them during a syncope recurrence) and to exclude the arrhythmic origin of the syncope in additional 19 (17%) patients. LG-ICM guided the implantation of a CIED in 16 (15%) US patients, due to the diagnosis of asystole or severe bradycardia. Age ≥ 65 years (p = 0.012) and atrial arrhythmia history (p = 0.004) are significant independent predictors of arrhythmic diagnoses performed by LG-ICM, while CAD is predictor of syncope recurrence (bordering on statistical significance, p = 0.056). CONCLUSIONS: The diagnostic yield of LG-ICM in US syncope is comparable to those of ILR and previous generation ICM. The advantages of LG-ICM should be sought in lower hospital workload necessary to manage ICM data. Age ≥ 65 years and atrial arrhythmia history are independent predictors of significant ICM-detected arrhythmias.

[New frontiers in pacing: from myocardial pacing to conduction system pacing]. / Nuove frontiere dell'elettrostimolazione: dal pacing del miocardio comune al pacing del sistema di conduzione.

For many years, cardiac pacing has been based on the stimulation of right ventricular common myocardium to correct diseases of the conduction system. The birth and the development of cardiac resynchronization have led to growing interest in the correction and prevention of pacing-induced dyssynchrony. Many observational studies and some randomized clinical trials have shown that conduction system pacing (CSP) can not only prevent pacing-induced dyssynchrony but can also correct proximal conduction system blocks, with reduction of QRS duration and with equal or greater effectiveness than biventricular pacing. Based on these results, many Italian electrophysiologists have changed the stimulation target from the right ventricular common myocardium to CSP. The two techniques with greater clinical impact are the His bundle stimulation and the left bundle branch pacing. The latter, in particular, because of its easier implantation technique and better electric parameters, is spreading like wildfire and is representing a real revolution in the cardiac pacing field. However, despite the growing amount of data, until now, the European Society of Cardiology guidelines give a very limited role to CSP.

Cardiopulmonary Bypass Settings for the Prevention of Early Hypotension During CABG.

BACKGROUND: Vasoplegic syndrome is a form of vasodilatory shock that can occur before, during or after cardiopulmonary bypass (CPB). We introduce a strategy to reduce the incidence of early hypotension phenomena during Coronary Artery Bypass Graft (CABG) procedures. MATERIALS AND METHODS: In this prospective cohort study, 100 patients underwent elective CABG with two perioperative CPB settings. The study group (50 patients) was managed with retrograde autologous priming (RAP), 3-minute stepwise for the institution of CPB, and pulsatile flow (PP). The control group (50 patients) was managed without RAP, with the rapid initiation of CPB, and non-pulsatile (NP) flow. The primary endpoints were MAP (mmHg), number of hypotensive phenomena (MAP < 50 mmHg for > 30 sec), the venous return volume on CPB (ml), the cardiac index (L/min/m2), hemoglobin (g/dL), indexed oxygen delivery (DO2i, ml/min/m2), the systemic vascular resistance index (SVRI, dynes s m2/cm5), number of 1-ml boluses of a vasoactive substance (norepinephrine), the positive fluid balance (ml), and the number of red blood cell units for transfusion. RESULTS: During CPB, the mean values in the study and control groups were as follows: MAP, 68± 7 vs 56 ± 7 (p-value, 0.0019); hypotensive phenomena, 3 ± 1 vs 8 ±2 (p-value, 0.019); venous return volume, 840±79 vs 1129 ±123 (p-value, 0.0017); cardiac index, 2.4 ± 0.4 vs 2.7 ±0.2 (p-value, 0.0023); hemoglobin, 9.13 ± 0.29 vs 7.8± 0.23 (p-value, 0.0001); DO2i, 301± 12 vs 276±23 (p-value, 0.0011); SVRI, 1879 ±280 vs 2210 ±140 (p-value, 0.0017); norepinephrine, 1±2 vs 8 ±3 (p-value, 0.0023); positive fluid balance, 750 ±212 vs 1450 ±220 (p-value, 0.005); and total number of red blood cell units for transfusion, 16 ±4.2 vs 27 ± 5.3 (p-value, 0.008). CONCLUSIONS: In this prospective cohort study, during CPB, the study group showed a better preservation of MAP, SVRI, and DO2i, and a reduction of vasoconstrictor use in a CPB setting with the RAP technique, 3-minute stepwise for the initiation of CPB and pulsatile pump flow, compared to the control group. Further studies are needed to validate this perioperative approach to CPB.

Short-term effect of sacubitril/valsartan on endothelial dysfunction and arterial stiffness in patients with chronic heart failure.

Heart failure (HF) is associated to endothelial dysfunction that promotes the increase of arterial stiffness thus augmenting myocardial damage. Sacubitril/Valsartan is used in the treatment of HF reduced ejection fraction (HFrEF) and has been proven effective in reducing cardiovascular disease (CVD) progression and all-cause mortality. The aim of this study was to evaluate the effect of Sacubitril/Valsartan on endothelial dysfunction, arterial stiffness, oxidative stress levels and platelets activation in patients with HFrEF, at baseline and after 6 months of treatment. We enrolled 100 Caucasian patients. Endothelial function was evaluated by the reactive hyperemia index (RHI) and arterial stiffness (AS) by the measurement of carotid-femoral pulse wave velocity (PWV), augmentation pressure (AP) and augmentation index (AI). At baseline, among enrolled outpatients, 43% showed a NYHA class II and 57% a NYHA class III. At 6 months, there was a significant improvement of several hemodynamic, clinical and metabolic parameters with a significant reduction in oxidative stress indices such as 8-isoprostane (p < 0.0001) and Nox-2 (p < 0.0001), platelets activity biomarkers such as sP-selectin (p < 0.0001) and Glycoprotein-VI (p < 0.0001), and inflammatory indices. Moreover, we observed a significant improvement in arterial stiffness parameters and in endothelial function indices. Our study demonstrated that 6 months treatment with Sacubitril/Valsartan, in patients with HFrEF, improves endothelial dysfunction and arterial stiffness, by reducing oxidative stress, platelet activation and inflammation circulating biomarkers, without adverse effects.

Ablation of paroxysmal and persistent atrial fibrillation with multielectrode phased radiofrequency duty-cycled catheters: long-term results from a large cohort of patients.

BACKGROUND: Catheter ablation is a widely used approach to treat patients with drug refractory paroxysmal atrial fibrillation (PAF) and persistent atrial fibrillation (CAF). The aim of this analysis was to evaluate the long-term safety and efficacy of the multielectrode/phased radiofrequency (RF)/duty-cycled ablation catheters in the treatment of both PAF and CAF in a large cohort of patients. METHODS AND RESULTS: From July 2008 to February 2010, 429 consecutive drug refractory symptomatic patients (mean age 60 ± 12 years old, 58% men, 68% PAF, 32% CAF) were treated. Seventy-five patients had two procedures resulting in a total of 504 procedures (procedure mean time: 62 ± 15 min). Following ablation, 4-day continuous Holter monitoring was done every 3 months. Recurrence was defined as any atrial tachyarrhythmia of more than 30 s. At 3 months 97.4% of patients were off antiarrhythmic drugs. During a mean follow-up of 22 ± 5 months, freedom from AF recurrence was 68.5% (95% CI: 63.8-72.6) and higher for PAF than CAF patients. The risk of AF recurrence in PAF patients increased in the presence of hypertension, dyslipidemia, large left atrial diameter (LAD) and low ejection fraction. For CAF patients, the risk of AF recurrence increased with larger LAD and lower ejection fraction. Complications that resolved prior to discharge were observed in nine patients (2.1%) with no strokes/transient ischemic attacks (TIAs). CONCLUSION: The ablation of symptomatic PAF and CAF with multielectrode phased radiofrequency/duty-cycled ablation catheters shows long-term safety and effectiveness with relatively short procedure times.

Successful radiofrequency ablation determines atrio-ventricular remodelling and improves systo-diastolic function at tissue Doppler-imaging.

BACKGROUND: Clinical, echocardiographic results and determinants of atrial fibrillation (AF) recurrence following AF ablation during mitral valve surgery (AFAMVS) were evaluated. METHODS: Fifty-two patients undergoing radiofrequency AFAMVS between January 2003 and December 2005, underwent serial echocardiographies with tissue Doppler imaging to assess atrio-ventricular function. Recurrence of AF, hospital readmission, episodes of congestive heart failure (CHF) were recorded. Predictors for AF-recurrence were evaluated. RESULTS: At a 29.5+/-8.6 months of follow-up (100% complete), 78.8% patients were in sinus rhythm (SR). Freedom from AF-recurrence was 64.6+/-0.76%, from hospital readmission 88.9+/-0.47%, from CHF 91.6+/-0.63%. SR-patients demonstrated better freedom from hospital readmission (97.4 vs 60.6%; p=0.0003) and from CHF (100 vs 72.7%; p=0.008) during follow-up. At follow-up SR-patients demonstrated left atrial (preoperative 5.8+/-0.8 cm vs follow-up 5.1+/-0.9; p=0.013) and ventricular reverse remodelling (preoperative LVDd 5.7+/-1.1cm vs follow-up 5.2+/-1.1; p=0.048 - preoperative LVDs 4.0+/-1.4 vs follow-up 3.6+/-1.1; p=0.036). E/A ratio was normal in 73.1% (92.7% of SR-patients). TDI at the level of the left lateral annulus showed an improved left ventricular systole (Sm), and diastole (Em, E/Em) of SR-patients, compared with AF-patients (Sm 9.40+/-1.74 vs 7.72+/-1.5, p=0.0001; Em: 10.45+/-1.98 vs 7.68+/-0.72, p=0.001; E/Em: 0.07+/-0.02 vs 0.10+/-0.04, p=0.0001). Large preoperative atrial diameter (OR=5.81; p=0.002), preoperative NYHA-IV (OR=3.55; p=0.001), high diuretics at discharge (OR=1.27; p=0.03), tricuspid insufficiency at follow-up (OR=2.31; p=0.02) were independent predictors of AF-recurrence. CONCLUSIONS: Radiofrequency AFAMVS achieves 78.8% of SR recovery. Maintenance of SR improves clinic, haemodynamic and echocardiographic endpoints. Pre- and post-operative cardiac failure is the main determinant of AF-recurrence.

Effect of interaction between left ventricular dysfunction and endothelial function in hypertension.

Hypertension, one of the most important risk factors for cardiovascular diseases, is associated with both left ventricular hypertrophy and endothelial dysfunction. Both have been recently recognized as independent predictors of clinical events in different groups of patients. In fact, a dysfunctioning endothelium loses its antiatherosclerotic and antithrombotic action, and, therefore, promotes the atherosclerotic process. Similarly, cardiac hypertrophy is recognized as a powerful and independent risk factor for cardiovascular morbidity and mortality because it predisposes to arrhythmias and maximizes the consequences of acute myocardial ischemia. Recently, an evident interaction has been demonstrated between endothelial dysfunction and left ventricular mass. In particular, the coexistence of both left ventricular hypertrophy and endothelial dysfunction almost doubles the risk for future vascular events in hypertensives. Thus, in hypertensive patients, it is clinically useful to choose an aggressive therapeutic strategy--to reduce left ventricular mass and to improve endothelial function.

Interaction between vascular dysfunction and cardiac mass increases the risk of cardiovascular outcomes in essential hypertension.

AIMS: To investigate the additive prognostic impact of both forearm endothelial dysfunction and left ventricular mass (LVM) for future cardiovascular events. METHODS AND RESULTS: We enrolled 324 Caucasian, never treated, hypertensive outpatients. Endothelial function, by intra-arterial infusion of acetylcholine (ACh), and echocardiographic LVM were investigated. Patients were divided into tertiles on the basis of their increase in ACh-stimulated forearm blood flow (FBF) and LVM indexed by body surface area (LVMI). Cardiovascular events assessed were: fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, transient cerebral ischaemic attack, unstable angina, coronary revascularization procedures, and symptomatic aorto-iliac occlusive disease. During a mean follow-up of 45.2+/-23.6 months, there were 47 new cardiovascular events (3.8 events/100 patient-years). The event rate was 6.8, 2.8, and 1.6% in the tertiles of ACh-stimulated FBF (log-rank test, P=0.0009), and 1.4, 3.4, and 6.6% in the tertiles of LVMI (log-rank test, P=0.0002), respectively. Besides, a significant interaction was documented between FBF and LVMI. In fact, the cardiovascular risk increases up to 11.4% in patients with low FBF and high LVMI. CONCLUSION: For the first time, we demonstrate that the co-existence of LVH and endothelial dysfunction in hypertensive patients increases significantly the risk of subsequent cardiovascular events.

Effects of amino acid supplementation on left ventricular remodeling in patients with chronic heart failure with decreased systolic function and diabetes mellitus: rationale and design of a magnetic resonance imaging study.

A considerable number of patients with reduced systolic function caused by primary or ischemic cardiomyopathy have viable and noncontractile myocardium. This may be related to numerous and perhaps overlapping factors, such as chronic ischemia (stunning/hibernation), neurohormonal abnormalities, oxidative stress, metabolic imbalances, and/or nutritional depletion. Changes in myocardial substrate utilization have adverse effects on the metabolism of the viable but noncontractile myocardium. Shifting the energy substrate preference away from fatty acids and replenishing the tricarboxylic acid cycle components via amino acids rather than via fatty acids would increase adenosine triphosphate production, with positive effects on cellular metabolism. A proposed study design is described and will be piloted through the Effects of Diatrofen on Myocardial Function in Patients with Chronic Heart Failure trial (D-CHF), an evaluation of an oral amino acid supplementation treatment in outpatients with heart failure.

Reappraisal of beta-blocker therapy in the acute and chronic post-myocardial infarction period.

In patients presenting with acute myocardial infarction (MI), the early use of intravenous beta-blockade followed by short-term oral administration in the absence of reperfusion therapy has shown a modest reduction in mortality. In contrast, major reductions in mortality and reinfarction have been shown when beta-blockers have been used soon after an acute MI and continued long-term. These benefits were observed in trials conducted in the 1970s and 1980s, prior to the widespread use of reperfusion therapies, antiplatelet agents, and angiotensin-converting enzyme inhibitors; those trials excluded patients with postischemic heart failure. Recently, the CAPRICORN trial has shown a significant reduction in all-cause mortality and reinfarction in post-MI patients with systolic dysfunction, in response to carvedilol. In spite of compelling evidence supporting the use of beta-blockers in the post-MI setting, data published by the National Cooperative Cardiovascular Project have shown that fewer than half of all post-MI patients receive beta-blockers as long-term therapy. It appears that post-MI patients with perceived contraindications, such as advanced age, diabetes, heart failure, peripheral vascular disease, and/or chronic pulmonary obstructive disease, may derive a substantial benefit from the use of beta-blockers. Given the considerable evidence from randomized clinical trials, the use of beta-blockers is recommended in all post-MI patients without a contraindication, particularly in those with left ventricular systolic dysfunction.

Effects of simvastatin on walking performance and symptoms of intermittent claudication in hypercholesterolemic patients with peripheral vascular disease.

PURPOSE: To analyze the effects of short-term therapy with simvastatin on walking performance in hypercholesterolemic patients with peripheral vascular disease. METHODS: Eighty-six patients with peripheral arterial disease (Fontaine stage II), intermittent claudication, and total cholesterol levels >220 mg/dL were enrolled in a randomized, placebo-controlled, double-blind study. Forty-three patients were assigned to simvastatin (40 mg/d); the remaining 43 patients were assigned to placebo treatment. All patients underwent an exercise test and clinical examination, and completed a self-assessment questionnaire at 0, 3, and 6 months. Pain-free and total walking distance, resting and postexercise ankle-brachial indexes, and questionnaire scores were determined at each follow-up. RESULTS: At 6 months, the mean pain-free walking distance had increased 90 meters (95% confidence interval [CI]: 64 to 116 meters; P <0.005) more in the simvastatin group than in the placebo group. Similar results were seen for the total walking distance (mean between-group difference in the change, 126 meters; 95% CI: 101 to 151 meters; P <0.001), and for the ankle-brachial index at rest (mean, 0.09; 95% CI: 0.06 to 0.12; P <0.01) and after exercise (mean, 0.19; 95% CI: 0.14 to 0.24; P <0.005). There was also a greater improvement in claudication symptoms among patients treated with simvastatin. The effects on walking performance, ankle-brachial indexes, and questionnaire scores had also been significant at 3 months. CONCLUSION: High-dose short-term therapy with simvastatin may improve walking performance, ankle-brachial pressure indexes, and symptoms of claudication in hypercholesterolemic patients with peripheral vascular disease.