Uric acid levels are associated with endothelial dysfunction and severity of coronary atherosclerosis during a first episode of acute coronary syndrome.

The role of serum uric acid in coronary artery disease has been extensively investigated. It was suggested that serum uric acid level (SUA) is an independent predictor of endothelial dysfunction and related to coronary artery lesions. However, the relationship between SUA and severity of coronary atherosclerosis evaluated via endothelial dysfunction using peripheral arterial tone (PAT) and the reactive hyperhemia index (RHI) has not been investigated during a first episode of acute coronary syndrome (ACS). The aim of our study was to address this point. We prospectively enrolled 80 patients with a first episode of ACS in a single-center observational study. All patients underwent coronary angiography, evaluation of endothelial function via the RHI, and SUA measurement. The severity of the coronary artery lesion was assessed angiographically, and patients were classified in three groups based on the extent of disease and Gensini and SYNTAX scores. Endothelial function was considered abnormal if RHI < 1.67. We identified a linear correlation between SUA and RHI (R2 = 0.66 P < 0.001). In multivariable analyses, SUA remained associated with RHI, even after adjustment for traditional cardiovascular risk factors and renal function. SUA was associated with severity of coronary artery disease. SUA is associated with severity of coronary atherosclerosis in patients with asymptomatic hyperuricemia. This inexpensive, readily measured biological parameter may be useful to monitor ACS patients.

Ventricular Arrhythmia Occurrence and Compliance in Patients Treated With the Wearable Cardioverter Defibrillator Following Percutaneous Coronary Intervention.

BACKGROUND: The wearable cardioverter defibrillator (WCD) is a life-saving therapy in patients with high risk of arrhythmic death. We aimed to evaluate ventricular arrhythmia (VA) occurrence rate and compliance with the WCD during the first 90 days following myocardial revascularisation with percutaneous coronary intervention (PCI) in patients with left ventricular ejection fraction (LVEF) <30%. METHODS: From September 2015 to November 2016, clinical characteristics, WCD recordings and compliance data of the aforementioned subset of patients were prospectively collected. RESULTS: Twenty-four patients (men=20, 80%) were included in this analysis. Mean age was 56±10 years and mean LVEF at enrolment was 26.6±4.3%. During a mean wearing period of 3.0±1.3 months, two episodes of VA occurred in two patients (8.3%): one successfully treated with WCD shock and one with spontaneous termination. The mean and median daily use of the WCD was 21.5hours and 23.5hours a day, respectively. Eighteen patients (75%) wore the WCD more than 22hours a day. CONCLUSIONS: The rate of VA, during the WCD period use after myocardial revascularisation with PCI, was high in our study. Otherwise it underlined that patient compliance is critical during the WCD period use. Remote monitoring and patient education are keys to achieve good compliance.

Early and Late Atrial Arrhythmias After Lung Transplantation　- Incidence, Predictive Factors and Impact on Mortality.

BACKGROUND: Atrial arrhythmias (AAs) are frequent after lung transplantation (LT) and late postoperatively. Several predictive factors of early postoperative AAs after LT have been identified but those of late AAs remain unknown. Whether AA after LT affects mortality is still being debated. This study assessed in a large cohort of LT patients the incidence of AAs early and late after surgery, their predictive factors and their effect on mortality.Methods and Results:We studied 271 consecutive LT patients over 9 years. Mean follow-up was 2.9±2.4 years. 33% patients developed postoperative AAs. Age (odds ratio (OR) 2.35; confidence interval (CI) [1.31-4.24]; P=0.004) and chronic obstructive pulmonary disease (OR 2.13; CI [1.12-4.03]; P=0.02) were independent predictive factors of early AAs. Late AAs occurred 2.2±2.7 years after transplant in 8.8% of the patients. Pretransplant systolic pulmonary arterial pressure (PTsPAP) was the only independent predictive factor of late AA (OR 1.028; CI [1.001-1.056]; P=0.04). Double LT was associated with long-term freedom from atrial fibrillation (AF) but not from atrial flutter (AFL). Early and late AAs after surgery had no effect on mortality. Double LT was associated with better survival. CONCLUSIONS: Early AA following LT is common in contrast with the low occurrence of late, often organized, AA. Early and late AAs do not affect mortality. PTsPAP is an independent predictor of late AA. Double LT protects against late AF but not AFL.

High Risk of Sustained Ventricular Arrhythmia Recurrence After Acute Myocarditis.

Acute myocarditis is associated with cardiac arrhythmia in 25% of cases; a third of these arrhythmias are ventricular tachycardia (VT) or ventricular fibrillation (VF). The implantation of a cardiac defibrillator (ICD) following sustained ventricular arrhythmia remains controversial in these patients. We sought to assess the risk of major arrhythmic ventricular events (MAEs) over time in patients implanted with an ICD following sustained VT/VF in the acute phase of myocarditis compared to those implanted for VT/VF occurring on myocarditis sequelae. Our retrospective observational study included patients implanted with an ICD following VT/VF during acute myocarditis or VT/VF on myocarditis sequelae, from 2007 to 2017, in 15 French university hospitals. Over a median follow-up period of 3 years, MAE occurred in 11 (39%) patients of the acute myocarditis group and 24 (60%) patients of the myocarditis sequelae group. Kaplan-Meier MAE rate estimates at one and three years of follow-up were 19% and 45% in the acute group, and 43% and 64% in the sequelae group. Patients who experienced sustained ventricular arrhythmias during acute myocarditis had a very high risk of VT/VF recurrence during follow-up. These results show that the risk of MAE recurrence remains high after resolution of the acute episode.

Dynamic iron status after acute heart failure.

BACKGROUND: Iron deficiency (ID) is common in heart failure (HF), and is associated with unfavourable clinical outcomes. Although it is recommended to screen for ID in HF, there is no clear consensus on the optimal timing of its assessment. AIM: To analyse changes in iron status during a short-term follow-up in patients admitted for acute HF. METHODS: Iron status (serum ferritin concentration and transferrin saturation) was determined in 110 consecutive patients (median age: 81 years) admitted to a referral centre for acute HF, at three timepoints (admission, discharge and 1 month after discharge). ID was defined according to the guidelines. RESULTS: The prevalence rates of ID at admission, discharge and 1 month were, respectively, 75% (95% confidence interval [CI] 67-83%), 61% (95% CI: 52-70%), and 70% (95% CI: 61-79%) (P=0.008). Changes in prevalence were significant between admission and discharge (P=0.0018). Despite a similar ID prevalence at admission and 1 month (P=0.34), iron status changed in 25% of patients. Between admission and discharge, variation in C-reactive protein correlated significantly with that of ferritin (ρ=0.30; P=0.001). Advanced age, anaemia, low ferritin concentration and low creatinine clearance were associated with the persistence of ID from admission to 1 month. CONCLUSIONS: Iron status is dynamic in patients admitted for acute HF. Although ID was as frequent at admission as at 1 month after discharge, iron status varied in 25% of patients.

High incidence of atrial fibrillation in patients treated with ibrutinib.

Objective: Atrial fibrillation (AF) is one of the most common side effects of ibrutinib, a drug that has dramatically improved the prognosis of chronic B-cell malignancies such as chronic lymphocytic leukaemia (CLL). The true incidence of ibrutinib-related AF (IRAF) is not well known and its therapeutic management poses unique challenges especially due to the inherent risk of bleeding. We aimed to determine the incidence and predictors of IRAF, and to analyse its management and outcome. Methods: A standardised monitoring was applied at two cardio-oncology clinics in consecutive patients referred before and during ibrutinib therapy. The primary endpoint was the incidence of IRAF. The excess of AF incidence with ibrutinib was studied by comparing the incidence of IRAF with the expected incidence of AF in general population and in patients with CLL not exposed to ibrutinib. Results: 53 patients were included. The incidence of IRAF was 38% at 2 years and the risk was 15-fold higher than the AF risk in both the general population and patients with CLL not exposed to ibrutinib (p<0.0001). The majority of cases occurred in asymptomatic patients within the first 6 months. Left atrial volume index ≥40 mL/m2 at treatment initiation identified patients at high risk of developing IRAF. No major bleeding events occurred in patients on ibrutinib, although the majority of patients with IRAF were treated with anticoagulants. Conclusions: This cardio-oncology study showed that the risk of IRAF was much higher than previously reported. The majority of cases occurred in asymptomatic patients justifying close monitoring.

Impact of the time-to-treatment concept on the outcome of acute heart failure: A pilot study.

BACKGROUND: An optimal maximum time of 60minutes has been recommended in recent guidelines for the first evaluation and treatment of patients with acute heart failure (AHF); however, this has not been tested prospectively. AIM: To analyze the impact of a time-to-treatment (TTT) strategy of <60minutes on the in-hospital outcome of patients with AHF. METHODS: During a single 1-month period, we consecutively enrolled all patients hospitalized with AHF in a prospective cohort. In this pilot study, TTT was defined as the time between the first medical contact to the onset of the first medical intervention. The primary outcome was a composite including in-hospital death or worsening AHF. RESULTS: Of the 74 patients included, 23 (31%) had a TTT of <60minutes. Although these patients were more likely to have a more severe episode of AHF, the primary outcome occurred only in patients with a TTT of ≥60minutes. The primary outcome was significantly associated with a TTT of ≥60minutes (P=0.036), low systolic blood pressure (P<0.01), rales more than halfway up the lung fields (P=0.02), infectious precipitating factor (P=0.04) and high serum concentrations of B-type natriuretic peptide (P<0.01) and urea (P=0.03). No significant differences were observed in the rate of treatment-induced acute renal insufficiency or in the long-term rates of death or rehospitalization for heart failure according to TTT. CONCLUSIONS: This study suggests that the recently recommended TTT strategy of <60minutes in the setting of AHF might be associated with a better prognosis during hospitalization. Further large prospective works are needed to confirm these preliminary results, and to define more precisely which types of AHF could benefit from this strategy.

Prevalence and characteristics of coronary artery disease in heart failure with preserved and mid-range ejection fractions: A systematic angiography approach.

BACKGROUND: Guidelines recommend careful screening and treatment of coronary artery disease (CAD) in heart failure with preserved or mid-range ejection fraction (HFpEF/HFmEF). AIM: We aimed to determine the prevalence and characteristics of CAD using a prospective systematic coronary angiography approach. METHODS: A systematic coronary angiography protocol was applied in consecutive patients admitted for HFpEF/HFmEF during a 6-month period in a single centre. History of CAD and results of angiography, including revascularization, were reported. RESULTS: Of the 164 patients with HFpEF/HFmEF who were included, an angiography assessment was applied in 108 (66%) (median age: 79 years [interquartile range: 70-85 years]; 54% were women). In our analysis, 64% (95% confidence interval [CI] 55-73%) of patients had a significant coronary stenosis corresponding to a global CAD prevalence of 80% (95% CI 73-88%). The prevalence of CAD was similar for HFpEF and HFmEF. The left main coronary artery presented a significant stenosis in 6.5% of cases and 39% of patients had a two- or three-vessel disease. The rate of significant coronary stenosis was non-significantly higher in patients with a history of CAD. Patients with HFpEF/HFmEF with and without CAD did not differ in clinically meaningful ways, in terms of symptoms or laboratory and echocardiography results. This strategy led to complete revascularization in 36% of patients with significant stenosis and in 23% of all patients with HFpEF/HFmEF. CONCLUSIONS: Our study differs from others in that we used a systematic angiography approach. The results suggest a much higher prevalence of CAD in HFpEF/HFmEF than previously reported and should encourage clinicians to aggressively identify this co-morbidity.

Controlled sedation with midazolam and analgesia with nalbuphine to alleviate pain in patients undergoing subcutaneous implantable cardioverter defibrillator implantation.

PURPOSE: Subcutaneous implantable cardioverter defibrillator (S-ICD) is an alternative to transvenous ICD to prevent sudden cardiac death. Subcutaneous ICD implantation frequently requires general anesthesia because of procedure nociceptive steps during creation of a large device pocket and lead tunneling. This study aims to determine if a strategy of operator-guided controlled sedation with midazolam and analgesia with nalbuphine is effective in alleviating pain during S-ICD implantation. METHODS: This prospective study included consecutive patients undergoing S-ICD implantation under controlled sedation with midazolam and combined analgesia with nalbuphine. The Critical-Care Pain Observation Tool (CPOT), a behavioral pain scale, was used for pain assessment during S-ICD placement and the Numeric Rate Scale (NRS) was used for evaluation of pain recollection after patient recovery. CPOT score of 3 or above and NRS score of 4 or above are considered to be associated with significant pain. RESULTS: Sixteen patients were included in this study: Ten men (62.5%) and six women with a mean age of 54 ± 11 years. Indication for S-ICD implantation was primary prevention in 11 patients (68.8%). Mean dose of administrated midazolam and nalbuphine was 0.11 ± 0.03 and 0.27 ± 0.05 mg/kg, respectively. Mean CPOT during the whole procedure was 1.4 ± 1.6. No patient presented procedural pain recollection as all 16 patients had NRS score less than 4. No serious adverse event related to sedation occurred during S-ICD implantation. CONCLUSIONS: This study suggests that operator-guided controlled sedation with midazolam and analgesia with nalbuphine is effective to alleviate procedural pain in patients undergoing S-ICD implantation and may constitute an alternative to general anesthesia.

Wearable cardioverter defibrillator: Bridge or alternative to implantation?

The implantable cardioverter-defibrillator (ICD) is effective to prevent sudden cardiac death (SCD) in selected patients with heart disease known to be at high risk for ventricular arrhythmia. Nevertheless, this invasive and definitive therapy is not indicated in patients with potentially transient or reversible causes of sudden death, or in patients with temporary contra-indication for ICD placement. The wearable cardioverter defibrillator (WCD) is increasingly used for SCD prevention both in patients awaiting ICD implantation or with an estimated high risk of ventricular arrhythmia though to be transient. We conducted a review of current clinical uses and benefits of the WCD, and described its technical aspects, limitations and perspectives.

Practices in management of cancer treatment-related cardiovascular toxicity: A cardio-oncology survey.

BACKGROUND: Cardiovascular toxicity has become a challenging issue during cancer therapy. Nonetheless, there is a lack of consensual guidelines for their management. We aimed to determine the current practices of oncologists regarding cardiovascular toxicity related to anthracyclines, trastuzumab and angiogenic inhibitors and to gather their opinions on the development of cardio-oncology programs. METHODS: A cross-sectional declarative study was submitted to French oncologists in the form of an individual, structured questionnaire. RESULTS: A total of 303 oncologists responded to the survey. Ninety-nine percent of oncologists prescribed cardiotoxic therapies, including anthracyclines (83%), trastuzumab (51%) and other angiogenic inhibitors (64%). The method adopted for managing cardiovascular toxicity was based on guidelines from expert oncology societies for only 35% of oncologists. None was aware of recommendations from expert cardiology societies. Prescription of pre-, peri- and post-therapy cardiovascular assessment was inconsistent and significantly less frequent for all classes of angiogenic inhibitors than for anthracyclines and trastuzumab (P<0.0001). Relative to pre-therapy assessment, post-therapy assessment was prescribed significantly less often for all cancer therapies (P<0.0001). Attitudes regarding the onset of left ventricular dysfunction were much more inconsistent when angiogenic inhibitors were involved. Additionally, the management of hypertension and QT prolongation was also inconsistent. Finally, 88% of oncologists supported projects of cardio-oncology programs development. CONCLUSIONS: Practices of oncologists are disparate in the field of cardiovascular toxicity. This finding underlines the complexity of managing many different situations and the need for distribution of formal guidelines from oncology and cardiology expert societies. The development of personalized cardio-oncology programs seems essential.

Vagal Reactions during Cryoballoon-Based Pulmonary Vein Isolation: A Clue for Autonomic Nervous System Modulation?

Although paroxysmal atrial fibrillation (AF) is known to be initiated by rapid firing of pulmonary veins (PV) and non-PV triggers, the crucial role of cardiac autonomic nervous system (ANS) in the initiation and maintenance of AF has long been appreciated in both experimental and clinical studies. The cardiac intrinsic ANS is composed of ganglionated plexi (GPs), located close to the left atrium-pulmonary vein junctions and a vast network of interconnecting neurons. Ablation strategies aiming for complete PV isolation (PVI) remain the cornerstone of AF ablation procedures. However, several observational studies and few randomized studies have suggested that GP ablation, as an adjunctive strategy, might achieve better clinical outcomes in patients undergoing radiofrequency-based PVI for both paroxysmal and nonparoxysmal AF. In these patients, vagal reactions (VR) such as vagally mediated bradycardia or asystole are thought to reflect intrinsic cardiac ANS modulation and/or denervation. Vagal reactions occurring during cryoballoon- (CB-) based PVI have been previously reported; however, little is known on resulting ANS modulation and/or prevalence and significance of vagal reactions during PVI with the CB technique. We conducted a review of prevalence, putative mechanisms, and significance of VR during CB-based PVI.

Management and research in cancer treatment-related cardiovascular toxicity: Challenges and perspectives.

Cardiovascular toxicity is a potentially serious complication that can result from the use of various cancer therapies and can impact the short- and long-term prognosis of treated patients as well as cancer survivors. In addition to their potential acute cardiovascular adverse events, new treatments can lead to late toxicity even after their completion because patients who survive longer generally have an increased exposure to the cancer therapies combined to standard cardiovascular risk factors. These complications expose the patient to the risk of cardiovascular morbi-mortality, which makes managing cardiovascular toxicity a significant challenge. Cardio-oncology programs offer the opportunity to improve cardiovascular monitoring, safety, and management through a better understanding of the pathogenesis of toxicity and interdisciplinary collaborations. In this review, we address new challenges, perspectives, and research priorities in cancer therapy-related cardiovascular toxicity to identify strategies that could improve the overall prognosis and survival of cancer patients. We also focus our discussion on the contribution of cardio-oncology in each step of the development and use of cancer therapies.