Comparing cardiovascular adverse events in cancer patients: A meta-analysis of combination therapy with angiogenesis inhibitors and immune checkpoint inhibitors versus angiogenesis inhibitors alone.

Anti-VEGF (vascular endothelial growth factor) agents were associated with increased risk of several cardiovascular events, while one meta-analysis did not show any significantly increased risk of cardiotoxicity associated with the use of immune checkpoint inhibitors (ICIs). This meta-analysis of randomized-controlled trials (RCTs) was designed to compare cardiovascular toxicity of anti-VEGF agents plus ICI vs anti-VEGF agents without ICIs. A systematic search of the literature was conducted to include all full papers reporting about phase II and III randomized controlled trials (RCTs) conducted in patients with solid malignancies randomized to an anti-VEGF agent plus an ICI vs. an anti-VEGF agent without an ICI. Overall incidences of cardiovascular events were compared between these two treatment groups estimating the corresponding odds ratios. This analysis suggests that ICIs may increase the risk of cardiovascular toxicities associated with anti-VEGF therapies. Further research, including real world studies, is warranted.

Targeting Bachmann's bundle in hybrid ablation for long-standing persistent atrial fibrillation: a proof of concept study.

BACKGROUND: Catheter-based or surgical procedures in patients with long-standing persistent atrial fibrillation (LSPAF) remain a challenge. As a result, different approaches including hybrid (surgical and endocardial) ablation have been developed. Bachmann's bundle (BB) is a mainly epicardial structure capable of sustaining arrhythmic reentry that could be involved in the development and perpetuation of atrial fibrillation. We investigated the efficacy and safety of an adjunctive BB ablation in LSPAF patients undergoing hybrid ablation. METHODS: In a two-arm non-randomized study, consecutive LSPAF patients undergoing epicardial isolation of pulmonary veins with left atrial posterior wall (box lesion) with (n = 30, BB group) and without additional BB ablation (n = 30, CONV group) were enrolled in the study. All patients underwent an endocardial procedure within 6 weeks post-surgery to assess for potential lesion gaps and additional atrial substrate modification. The primary endpoint was freedom from AF through 12 months of follow-up. RESULTS: The two-staged hybrid ablation was successfully completed in all patients. One-year freedom from atrial arrhythmias recurrence rates was 96.6% in the BB group vs 76.6% in the CONV group (p = 0.025). At procedure completion, 30 (100%) and 17 (56%) patients had a spontaneous cardioversion in BB and CONV group, respectively (p < 0.001). No significant differences in quality of life or complication rates were observed. CONCLUSIONS: This initial experience shows, for the first time, that adjunctive BB ablation in the setting of hybrid ablation for LSPAF is a feasible and effective approach in increasing maintenance of sinus rhythm without increasing complication rates.

Stepwise endo-/epicardial catheter ablation for atrial fibrillation: The Mediterranea approach.

BACKGROUND: Outcomes of catheter ablation (CA) among patients with nonparoxysmal atrial fibrillation (AF) are largely disappointing. OBJECTIVE: We sought to evaluate the feasibility, effectiveness, and safety of a single-stage stepwise endo-/epicardial approach in patients with persistent/longstanding-persistent AF. METHODS: We enrolled 25 consecutive patients with symptomatic persistent (n = 4) or longstanding-persistent (n = 21) AF and at least one prior endocardial procedure, who underwent CA using an endo-/epicardial approach. Our anatomical stepwise protocol included multiple endocardial as well as epicardial (Bachmann's bundle [BB] and ligament of Marshall ablations) components, and entailed ablation of atrial tachycardias emerging during the procedure. The primary outcome was freedom from any AF/atrial tachycardia episode after a 3-month blanking period. The secondary outcome was patients' symptom status during follow-up. RESULTS: The stepwise endo-/epicardial approach allowed sinus rhythm restoration in 72% of patients, either directly (n = 6, 24%) or after AF organization into atrial tachycardia (n = 12, 48%). BB's ablation was commonly implicated in arrhythmia termination. After a median follow-up of 266 days (interquartile range, 96 days), survival free from AF/atrial tachycardia was 88%. Antiarrhythmic drugs could be discontinued in 22 patients (88%). As compared to baseline, more patients were asymptomatic at 9-month follow-up (0% vs. 56%, p = .02). Five patients (20%) developed mild medical complications, whereas one subject (4%) had severe kidney injury requiring dialysis. CONCLUSION: A single-stage endo-/epicardial CA resulted in favorable rhythm and symptom outcomes in a cohort of patients with symptomatic persistent/longstanding-persistent AF and one or more prior endocardial procedures. Epicardial ablation of BB was commonly implicated in procedural success.

Assessing the Malignant Ventricular Arrhythmic Substrate in Patients With Brugada Syndrome.

BACKGROUND: Guidelines recommend the use of implanted cardioverter-defibrillators in patients with Brugada syndrome and induced ventricular tachyarrhythmias, but there is no evidence supporting it. OBJECTIVES: This prospective registry study was designed to explore clinical and electrophysiological predictors of malignant ventricular tachyarrhythmia inducibility in Brugada syndrome. METHODS: A total of 191 consecutive selected patients with (group 1; n = 88) and without (group 2; n = 103) Brugada syndrome-related symptoms were prospectively enrolled in the registry. Patients underwent electrophysiological study and substrate mapping or ablation before and after ajmaline testing (1 mg/kg/5 min). RESULTS: Overall, before ajmaline testing, 53.4% of patients had ventricular tachyarrhythmia inducibility, which was more frequent in group 1 (65.9%) than in group 2 (42.7%; p < 0.001). Regardless of clinical presentation, larger substrates with more fragmented long-duration ventricular potentials were found in patients with inducible arrhythmias than in patients without inducible arrhythmias (p < 0.001). One extrastimulus was used in more extensive substrates (median 13 cm2; p < 0.001), and ventricular fibrillation was the more frequently induced rhythm (p < 0.001). After ajmaline, patients without arrhythmia inducibility had arrhythmia inducibility without a difference in substrate characteristics between the 2 groups. The substrate size was the only independent predictor of inducibility (odds ratio: 4.51; 95% confidence interval: 2.51 to 8.09; p < 0.001). A substrate size of 4 cm2 best identified patients with inducible arrhythmias (area under the curve: 0.98; p < 0.001). Substrate ablation prevented ventricular tachyarrhythmia reinducibility. CONCLUSIONS: In Brugada syndrome dynamic substrate variability represents the pathophysiological basis of lethal ventricular tachyarrhythmias. Substrate size is independently associated with arrhythmia inducibility, and its determination after ajmaline identifies high-risk patients missed by clinical criteria. Substrate ablation is associated with electrocardiogram normalization and not arrhythmia reinducibility. (Epicardial Ablation in Brugada Syndrome [BRUGADA_I]; NCT02641431; Epicardial Ablation in Brugada Syndrome: An Extension Study of 200 BrS Patients; NCT03106701).

Nuclear imaging in detection and monitoring of cardiotoxicity.

Cardiotoxicity as a result of cancer treatment is a novel and serious public health issue that has a significant impact on a cancer patient's management and outcome. The coexistence of cancer and cardiac disease in the same patient is more common because of aging population and improvements in the efficacy of antitumor agents. Left ventricular dysfunction is the most typical manifestation and can lead to heart failure. Left ventricular ejection fraction measurement by echocardiography and multigated radionuclide angiography is the most common diagnostic approach to detect cardiac damage, but it identifies a late manifestation of myocardial injury. Early non-invasive imaging techniques are needed for the diagnosis and monitoring of cardiotoxic effects. Although echocardiography and cardiac magnetic resonance are the most commonly used imaging techniques for cardiotoxicity assessment, greater attention is focused on new nuclear cardiologic techniques, which can identify high-risk patients in the early stage and visualize the pathophysiologic process at the tissue level before clinical manifestation. The aim of this review is to summarize the role of nuclear imaging techniques in the non-invasive detection of myocardial damage related to antineoplastic therapy at the reversible stage, focusing on the current role and future perspectives of nuclear imaging techniques and molecular radiotracers in detection and monitoring of cardiotoxicity.

Effects of ranolazine in symptomatic patients with stable coronary artery disease. A systematic review and meta-analysis.

BACKGROUND: Ranolazine (R), as add-on therapy in symptomatic patients with chronic stable coronary artery disease (CAD), has been tested in randomized clinical studies. Aim of the study was to assess in a meta-analysis the effects of R on angina, nitroglycerin consumption, functional capacity, electrocardiographic signs of ischemia and hemodynamic parameters in patients with chronic CAD. METHODS: Randomized trials assessing the effects of R compared to control on exercise duration, time to onset of angina, time to 1mm ST-segment depression, weekly nitroglycerin consumption and weekly angina frequency were included in the analysis. The effects of R compared to control on heart rate and blood pressure were also analyzed. RESULTS: Six trials enrolling 9223 patients were included in the analysis. At trough and peak levels, R compared to control significantly improved exercise duration, time to onset of angina and time to 1mm ST-segment depression. Additionally, R compared to control significantly reduced weekly angina frequency and weekly nitroglycerin consumption. Finally, R compared to control did not significantly reduce supine systolic and diastolic blood pressure as well as heart rate, standing heart rate and diastolic blood pressure, whereas it modestly reduced standing systolic blood pressure. At sensitivity analysis, results were not influenced by concomitant background therapy. CONCLUSIONS: In symptomatic patients with chronic CAD, R, added to conventional therapy, effectively reduces angina frequency and sublingual nitroglycerin consumption while prolonging exercise duration as well as time to onset of ischemia and to onset of angina with no substantial effects on blood pressure and heart rate.

[New perspectives in cardiovascular risk reduction: focus on HDL]. / Nuove prospettive nella riduzione del rischio cardiovascolare: focus su HDL.

Cardiovascular diseases represent the leading cause of morbidity and mortality worldwide, mostly contributing to hospitalizations and health care costs. Dyslipidemias represent one of the major cardiovascular risk factor and its management, throughout life-style modifications and pharmacological interventions, has shown to reduce cardiac events. The risk of adverse cardiovascular events is related not only to elevated LDL blood levels, but also to decreased HDL concentrations, that exhibit protective effects in the development of atherosclerotic process. Aim of this review is to summarize current evidences about defensing effects of such lipoproteins and to show the most recent pharmacological strategies to reduce cardiovascular risk through the increase of their circulating levels.

[Cardiovascular risk in systemic inflammatory diseases]. / Il rischio cardiovascolare nelle patologie infiammatorie sistemiche.

Systemic inflammatory diseases are associated with increased cardiovascular morbidity and mortality. The link between inflammatory and cardiovascular diseases can be attributed to the coexistence of classical risk factors and inflammatory mechanisms activated during systemic inflammatory diseases involving the immune system. Unfavorable metabolic effects of anti-inflammatory drugs can also contribute to increase cardiovascular risk. Yet, clinical implications of these findings are not entirely clear, and deeper knowledge and awareness of cardiac involvement in inflammatory diseases are necessary. The aim of this review is to summarize cardiac involvement in systemic inflammatory diseases and to identify aspects where evidence is currently lacking that would deserve further investigation in the future.

[Endothelial dysfunction in type 2 diabetic patients with normal coronary arteries. A peripheral arterial tonometry study]. / Evidenza di disfunzione endoteliale in pazienti diabetici di tipo 2 con arterie coronariche angiograficamente normali. Studio con tonometria arteriosa digitale.

AIM: to evaluate endothelial function (EF) in diabetic and non-diabetic patients without CAD by peripheral artery tonometry (PAT) technique. METHODS: a cohort of 94 patients (55 men and 39 postmenopausal women; mean age 63 +/- 9 years) undergoing coronary angiography was divided into 2 groups: 58 patients with DM and (group 1) and 36 patients without DM. Endothelial dysfunction (ED) was assessed by digital pulse amplitude, using a fingertip peripheral arterial tonometry (PAT). As a measure of ED, reactive hyperemia index (RHI) was calculated as the ratio of the digital pulse volume during reactive hyperemia following 5 min ischemia and its basal value. RESULTS: prevalence of cardiovascular risk factors was similar between the two groups. RHI values were significantly lower in diabetic patients compared to non-diabetics (1.72 +/- 0.34 vs 2.00 +/- 0.44; p < 0.005) and they correlated with levels of glycosylated hemoglobin (p = 0.05; r = -0.266). CONCLUSION: despite similar level of other risk factors, EF was much more impaired in diabetic patients than in non-diabetics. These evidences further support the impact of DM on cardiovascular risk.

[Metabolic and cardiovascular effects of combined antiretroviral therapy in patients with HIV infection. Systematic review of literature]. / Effetti metabolici e cardiovascolari della terapia antiretrovirale combinata in pazienti con infezione da HIV. Rassegna sistematica della letteratura.

In HIV infected patients an increased incidence of cardiac events has been reported since the introduction of highly active antiretroviral therapy (HAART). Antiretroviral drugs' regimens are, in fact, associated with several metabolic side effects, such as dyslipidemia, impaired glucose metabolism and abnormal body fat distribution, that increase cardiovascular risk of HIV subjects. In addition, HIV infection itself, the chronic inflammatory status and the frequent presence in this population of traditional risk factors contribute to an higher incidence of cardio and cerebrovascular events. In last years several studies showed the occurrence of carotid vascular impairment in patients treated with protease inhibitors (PI). Similarly the DAD Study reported an increase of 26% of the risk of myocardial infarction in patients on HAART and that this risk was independently associated with longer exposure to PI, after multivariate adjustments. A correct evaluation of the metabolic status before starting HAART and an adequate control of drugs-related metabolic abnormalities may reduce the incidence of cardiac events and still improve HIV patients prognosis. This review will focus on the metabolic effects of antiretroviral drugs and on the contribution of combination antiretroviral therapy on cardiovascular risk.