N-Acetylcysteine to Reduce Mortality for Patients Requiring Cardiac Catheterization or Cardiac Surgery: A Systematic Review and Meta-analysis.

ABSTRACT: Multimers of von Willebrand factor play a critical role in various processes inducing morbidity and mortality in cardiovascular-risk patients. With the ability to reduce von Willebrand factor multimers, N-acetylcysteine (NAC) could reduce mortality in patients undergoing coronary catheterization or cardiac surgery. However, its impact in perioperative period has never been studied so far in regard of its potential cardiovascular benefits. Then, 4 databases were searched for randomized controlled trials that compared in-hospital mortality between an experimental group, with NAC, and a control group without NAC, in patients undergoing coronary catheterization or cardiac surgery. The primary efficacy outcome was in-hospital mortality. Secondary outcomes were the occurrence of thrombotic events, major cardiovascular events, myocardial infarction, and contrast-induced nephropathy. The safety outcome was occurrence of hemorrhagic events. Nineteen studies totaling 3718 patients were included. Pooled analysis demonstrated a reduction of in-hospital mortality associated with NAC: odds ratio, 0.60; 95% confidence interval, 0.39-0.92; P = 0.02. The occurrence of secondary outcomes was not significantly reduced with NAC except for contrast-induced nephropathy. No difference was reported for hemorrhagic events. Subgroup analyses revealed a life-saving effect of NAC in a dose-dependent manner with reduction of in-hospital mortality for the NAC high-dose group, but not for the NAC standard-dose (<3500-mg) group. In conclusion, without being able to conclude on the nature of the mechanism involved, our review suggests a benefit of NAC in cardiovascular-risk patients in perioperative period in terms of mortality and supports prospective confirmatory studies.

Definition of left ventricular remodelling following ST-elevation myocardial infarction: a systematic review of cardiac magnetic resonance studies in the past decade.

An increase in left ventricular volumes between baseline and follow-up imaging is the main criteria for the quantification of left ventricular remodelling (LVR) after ST-elevation myocardial infarction (STEMI), but without consensual definition. We aimed to review the criteria used for the definition of LVR based on cardiac magnetic resonance imaging (CMR) in STEMI patients. A systematic literature search was conducted using MEDLINE and the Cochrane Library from January 2010 to August 2019. Thirty-seven studies involving 4209 patients were included. Among these studies, 30 (81%) used a cut-off value for defining LVR, with a pooled LVR prevalence estimate of 22.8%, 95% CI [19.4-26.7%] and a major between-study heterogeneity (I2 = 82%). The seven remaining studies (19%) defined LVR as a continuous variable. The definition of LVR using CMR following STEMI is highly variable, among studies including highly selected patients. A 20% increase or a 15% increase in left ventricular volumes between a baseline and a follow-up CMR imaging were the two most common criterion (13 [35%] and 9 [24%] studies, respectively). The most frequent LVR criterion was a 20% increase in end-diastolic volumes or a 15% increase in end-systolic volumes. A composite cut-off value of a 12 to 15% increase in end-systolic volume and a 12 to 20% increase in end-diastolic volume using a follow-up CMR imaging 3 months after STEMI might be proposed as a consensual cut-off for defining adverse LVR for future large-sized, prospective studies with serial CMR imaging and long-term follow-up in unselected patients.

A telemonitoring programme in patients with heart failure in France: a cost-utility analysis.

BACKGROUND: Certain telemedicine programmes for heart failure (HF) have been shown to reduce all-cause mortality and heart failure-related hospitalisations, but their cost-effectiveness remains controversial. The SCAD programme is a home-based interactive telemonitoring service for HF, which is one of the largest and longest-running telemonitoring programmes for HF in France. The objective of this cost-utility analysis was to evaluate the cost-effectiveness of the SCAD programme with respect to standard hospital-based care in patients with HF. METHODS: A Markov model simulating hospitalisations and mortality in patients with HF was constructed to estimate outcomes and costs. The model included six distinct health states (three 'not hospitalised' states, two 'hospitalisation for heart failure' states, both depending on the number of previous hospitalisations, and one death state). The model lifetime in the base case was 10 years. Model inputs were based on published literature. Outputs (costs and QALYs) were compared between SCAD participants and standard care. Deterministic and probabilistic sensitivity analyses were performed to assess uncertainty in the input parameters of the model. RESULTS: The number of quality-adjusted life years (QALYs) was 3.75 in the standard care setting and 4.41 in the SCAD setting. This corresponds to a gain in QALYs provided by the SCAD programme of 0.65 over the 10 years lifetime of the model. The estimated total cost was €30,932 in the standard care setting and €35,177 in the SCAD setting, with an incremental cost of €4245. The incremental cost-effectiveness ratio (ICER) for the SCAD programme over standard care was estimated at €4579/QALY. In the deterministic sensitivity analysis, the variables that had the most impact on the ICER were HF management costs. The likelihood of the SCAD programme being considered cost-effective was 90% at a willingness-to-pay threshold of €11,800. CONCLUSIONS: Enrolment of patients into the SCAD programme is highly cost-effective. Extension of the programme to other hospitals and more patients would have a limited budget impact but provide important clinical benefits. This finding should also be taken into account in new public health policies aimed at encouraging a shift from inpatient to ambulatory care.

Left atrial strain quantified after myocardial infarction is associated with early left ventricular remodeling.

BACKGROUND: Left ventricular remodeling (LVR) is common and associated with adverse outcome after ST-elevation myocardial infarction (STEMI). We aimed to investigate the association between left atrial (LA) mechanical function using speckle tracking imaging and early LVR at follow-up in STEMI patients. METHODS: Baseline 3D thoracic echocardiograms were performed within 48 h following admission and at a median follow-up of 7 months after STEMI. A > 20% increase in the left ventricular (LV) end-diastolic volume compared to baseline at follow-up was defined as LVR. LA global longitudinal strain was evaluated for the reservoir, conduit, and contraction (LASct) phases. RESULTS: A total of 121 patients without clinical heart failure (HF) were prospectively included, between June 2015 and October 2018 (age 58.3 ± 12.5 years, male 98 (81%)). Baseline and follow-up LV ejection fraction (LVEF) were 46.8% [41.0, 52.9] and 52.1% [45.8, 57.0] respectively (p < .001). Compared to other patients, those with LVR had significantly lower values of LASct at baseline (-7.4% [-10.1, -6.5] vs. -9.9% [-12.8, -8.1], p < .01), both on univariate and baseline LV volumes-adjusted analyses. Baseline LA strain for reservoir and conduit phases were not associated with significant LVR at follow-up. Intra- and interobserver analysis showed good reproducibility of LA strain. CONCLUSIONS: Baseline LASct may help identifying patients without HF after STEMI who are at higher risk of further early LVR and subsequent HF and who may benefit from more intensive management.

Cardiovascular immunotoxicities associated with immune checkpoint inhibitors: a safety meta-analysis.

AIMS: The risk and incidence of cardiovascular (CV) immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) in cancer patients remain unknown. METHODS AND RESULTS: We systematically reviewed all randomized clinical trials (RCTs) including at least one ICI-containing arm and available CV adverse event (CVAE) data in cancer patients in the ClinicalTrials.gov registry, Medline, and the Cochrane CENTRAL Register of Controlled Trials, up to 31 August 2020 (CRD42020165672). The primary outcome was the summary risk of 16 different CVAEs associated with ICI exposure vs. controls (placebo and non-placebo) in RCTs. CVAEs with an increased risk associated with ICI exposure were considered as CV irAEs. Summary incidences of CV irAEs identified in our primary outcome analyses were computed using all RCTs including at least one ICI-containing arm. We used a random-effects meta-analysis to obtain Peto odds ratios (ORs) with 95% confidence intervals (CIs) and logit transformation and inverse variance weighting to compute summary incidences. Sixty-three unique RCTs with at least one ICI-containing arm (32 518 patients) were retrieved, among which 48 (29 592 patients) had a control arm. Among the 16 CVAEs studied, ICI use was associated with an increased risk of 6 CV irAEs including myocarditis, pericardial diseases, heart failure, dyslipidemia, myocardial infarction, and cerebral arterial ischaemia with higher risks for myocarditis (Peto OR: 4.42, 95% CI: 1.56-12.50, P < 0.01; I2 = 0%, P = 0.93) and dyslipidemia (Peto OR: 3.68, 95% CI: 1.89-7.19, P < 0.01; I2 = 0%, P = 0.66). The incidence of these CVAEs ranged from 3.2 (95% CI 2.0-5.1) to 19.3 (6.7-54.1) per 1000 patients, in studies with a median follow-up ranging from 3.2 to 32.8 months. CONCLUSION: In RCTs, ICI use was associated with six CV irAEs, not confined to myocarditis and pericarditis.

Association Between Use of Anticancer Drugs and Cardiovascular Disease-Related Hospitalization in Metastatic Colorectal Cancer: Insights From a Population-Based Study, the Anticancer Vigilance of Cardiac Events Study.

We aimed to investigate the association between use of anticancer drugs and cardiovascular-related hospitalization (CVRH) among patients with metastatic colorectal cancer (mCRC). A cohort study, the Anticancer Vigilance of Cardiac Events (AVOCETTE) Study, was conducted using data from the digestive tumor registry of a French county, the Département du Calvados. Incident mCRC cases diagnosed between 2008 and 2014 were included. The follow-up end date was December 31, 2016. Data from the county hospital center pharmacy and medical information departments were matched with the registry data. A competing-risks approach was used. Statistical tests were 2-sided. A total of 1,116 mCRC patients were included, and they were administered 12,374 rounds of treatment; fluorouracil, oxaliplatin, irinotecan, and bevacizumab were most common drugs used. A total of 208 CVRH events occurred in 145 patients (13.0%). The International Cancer Survival Standards type 1 standardized incidence was 84.0 CVRH per 1,000 person-years (95% confidence interval: 72.6, 95.5). Anticancer drugs were not associated with a higher incidence of CVRH. Male sex, increasing age, a prior history of CVRH, and a higher Charlson comorbidity index score were associated with a higher incidence of CVRH. CVRH was significantly associated with higher all-cause mortality (multivariable hazard ratio = 1.58, 95% confidence interval: 1.28, 1.95). In this study, anticancer drugs were not associated with a higher incidence of CVRH in mCRC patients.

Comparison of the dyssynchrony parameters recorded with gated SPECT in ischemic cardiomyopathy according to their repeatability at rest and to their ability to detect a synchrony reserve under dobutamine infusion.

BACKGROUND: This study aimed to determine whether the repeatability of dyssynchrony assessment using gated myocardial perfusion SPECT (GSPECT) allows the detection of synchrony reserve during low-dose dobutamine infusion. METHODS AND RESULTS: Sixty-one patients with ischemic cardiomyopathy and LV ejection fraction < 50% were prospectively included in 10 centers. Each patient underwent two consecutive rest GSPECT with 99mTc-labeled tracer (either tetrofosmin or sestamibi) to assess the repeatability of LV function and dyssynchrony parameters, followed by a GSECT acquisition during low-dose dobutamine infusion. LV dyssynchrony was assessed using QGS software through histogram bandwidth (BW), standard deviation of the phase (SD), and entropy. Repeatability was assessed with Lin's concordance correlation coefficient (CCC). Entropy showed a higher CCC (0.80) compared to BW (0.68) and SD (0.75). On average, dobutamine infusion yielded to improve both BW (P = .049) and entropy (P = .04) although significant improvements, setting outside the 95% confidence interval of the repeatability analysis, were documented in only 6 and 4 patients for BW and entropy, respectively. CONCLUSIONS: A synchrony reserve may be documented in patients with ischemic cardiomyopathy through the recording of BW and entropy with low-dose dobutamine GSPECT, with the additional advantage of a higher repeatability for entropy.

Atrial fibrillation detection by the subcutaneous defibrillator: real-world clinical performances and implications from a multicentre study.

AIMS: No data exist concerning the clinical performances of the subcutaneous implantable cardioverter-defibrillator (S-ICD) atrial fibrillation (AF) detection algorithm. We aimed to study the performances and implications of the latter in a 'real-world' setting. METHODS AND RESULTS: Between July 2017 and August 2019, 155 consecutive S-ICD recipients were included. Endpoint of the study was the incidence of de novo or recurrent AF using a combined on-site and remote-monitoring follow-up approach. After a mean follow-up of 13 ± 8 months, 2531 AF alerts were generated for 55 patients. A blinded analysis of the 1950 subcutaneous electrocardiograms available was performed. Among them 47% were true AF, 23% were premature atrial contractions or non-sustained AF, 29% were premature ventricular contractions or non-sustained ventricular tachycardia, and 1% were misdetection. Fourteen percent (21/155) patients had at least one correct diagnosis of AF by the S-ICD algorithm. One patient presented symptomatic paroxysmal AF not diagnosed by the S-ICD algorithm (false negative patient). Patient-based sensitivity, specificity, positive, and negative predictive values were respectively 95%, 74%, 38%, and 99%. Among patients with at least one correct diagnosis of AF, 38% (8/21) had subsequent clinical implications (anticoagulation initiation or rhythm control therapies). CONCLUSION: The S-ICD AF detection algorithm yields a high sensitivity for AF diagnosis. Low specificity and positive predictive value contribute to a high remote monitoring-notification workload and underline the necessity of a manual analysis. Atrial fibrillation diagnosis by the S-ICD AF detection algorithm might lead to significant therapeutic adjustments.

Serum neprilysin levels are associated with myocardial stunning after ST-elevation myocardial infarction.

BACKGROUND: Left ventricular remodeling following ST-elevation myocardial infarction (STEMI) is associated with poor outcome, including heart failure (HF). Neprilysin inhibition leads to improved outcome in patients with altered left ventricular ejection fraction (LVEF). METHODS: We aimed to assess the association between serum levels of neprilysin and left ventricular (LV) volumes, function and remodeling in STEMI patients with successful myocardial reperfusion and no clinical sign of HF. Sixty-eight patients were admitted for STEMI and had both plasma neprilysin measurement at baseline and 3D transthoracic echocardiogram at baseline and after a median follow-up of 7 months. We compared 3 groups: a group with a low-level of plasma neprilysin (< 125 pg/mL, i.e. the lower limit of detection of the assay) and the two other groups were defined as being below or above the median value of the remaining samples. RESULTS: Median age was 58.5 ± 12.8 years and 56 (82.4%) were men. Median LVEF was 45.0 ± 8.5%. Baseline characteristics were comparable between groups (low-level of neprilysin group [≤125 pg/mL, n = 38], medium-level of neprilysin group [126-450 pg/mL, n = 15] and a high-level group [> 450 pg/mL, n = 15]). At baseline there was a non-significant trend towards lower end-diastolic volume (p = 0.07) but significantly lower LVEF in the high neprilysin group (46.4 ± 8.3%, 47.1 ± 8.1% and 39.1 ± 6.9%, p < 0.01). At follow-up, the magnitude of LVEF increase was significantly more important in the high neprilysin group compared to the other groups (p = 0.022 for relative change in LVEF and 6.6 ± 7.3%, 3.6 ± 9.0% and 11.3 ± 8.4%, p = 0.031 for absolute change in LVEF) resulting in similar LVEF levels at follow-up between all groups (53.0 ± 8.9%, 50.6 ± 9.7% and 50.4 ± 9.9%, p = 0.55). CONCLUSIONS: Initial high neprilysin levels may identify patients with stunned myocardium early after STEMI, with a recovery of contractility leading to improved LVEF at follow-up. Future studies will have to assess the role of neprilysin in the setting of STEMI and the potential benefit of its blockade.

Spironolactone and perioperative atrial fibrillation occurrence in cardiac surgery patients: Rationale and design of the ALDOCURE trial.

BACKGROUND: After artery bypass grafting (CABG), the presence of perioperative AF (POAF) is associated with greater short- and long-term cardiovascular morbidity. Underlying POAF mechanisms are complex and include the presence of an arrhythmogenic substrate, cardiac fibrosis and electrical remodeling. Aldosterone is a key component in this process. We hypothesize that perioperative mineralocorticoid receptor (MR) blockade may decrease the POAF incidence in patients with a left ventricular ejection fraction (LVEF) ≥50% who are referred for CABG with or without aortic valve replacement (AVR). STUDY DESIGN: The ALDOCURE trial (NCT03551548) will be a multicenter, randomized, double-blind, placebo-controlled trial testing the superiority of a low-cost MR antagonist (MRA, spironolactone) on POAF in 1500 adults referred for on-pump elective CABG surgery with or without AVR, without any history of heart failure or atrial arrhythmia. The primary efficacy end point is the occurrence of POAF from randomization to within 5 days after surgery, assessed in a standardized manner. The main secondary efficacy end points include the following: postoperative AF occurring within 5 days after cardiac surgery, perioperative myocardial injury, major cardiovascular events and death occurring within 30 days of surgery, hospital and intensive care unit length of stay, need for readmission, LVEF at discharge and significant ventricular arrhythmias within 5 days after surgery. Safety end points, including blood pressure, serum potassium levels and renal function, will be monitored regularly throughout the trial duration. CONCLUSION: The ALDOCURE trial will assess the effectiveness of spironolactone in addition to standard therapy for reducing POAF in patients undergoing CABG. CLINICAL TRIAL REGISTRATION: NCT03551548.

Predictors of clinical outcomes after cardiac resynchronization therapy in patients ≥75 years of age: a retrospective cohort study.

BACKGROUND: Cardiac resynchronization therapy has been shown to benefit selected patients with heart failure and reduced ejection fraction. Older patients have been underrepresented in randomized trials. This study was conducted to determine whether predictive factors for cardiac resynchronization therapy outcomes differ in patients older and younger than 75 years of age. METHODS: Consecutive patients who received a cardiac resynchronization device cardiac resynchronization therapy between 2013 and 2016 in our center were retrospectively included in this cohort study. The primary endpoint was cardiac resynchronization therapy effectiveness, which was defined as survival for one year with both no heart failure hospitalization and improvement by one or more NYHA class. The secondary endpoints were mortality, complications, and device therapies. RESULTS: Among the 243 patients included, 102 were ≥ 75 years old. Cardiac resynchronization therapy effectiveness was observed in 70 patients (50%) < 75 years old and in 48 patients (47%) ≥75 years old (p = 0.69). NYHA class ≥III (OR = 6.02; CI95% [1.33-18.77], p = 0.002) was a predictive factor for cardiac resynchronization therapy effectiveness only in the ≥75-year-old group, while atrial fibrillation was independently negatively associated with the primary endpoint in the < 75-year-old group (OR = 0.28; CI95% [0.13-0.62], p = 0.001). The one-year mortality rate was 14%, with no difference between age groups. Rescue cardiac resynchronization therapy and atrial fibrillation were independent predictive factors for mortality in both age groups. Eighty-two complications occurred in 45 patients (19%), with no difference between groups. Defibrillator use and QRS duration were independent predictive factors for complications in both age groups. There was no difference between groups considering device therapies. CONCLUSION: At one year, cardiac resynchronization therapy response is not compromised by patient age. In older patients, highly symptomatic individuals with NYHA class ≥III have better outcomes after cardiac resynchronization therapy.

Antithrombotic Therapy for ACS in Elderly Patients.

BACKGROUND: Patients over 75 account for more than one third of those presenting with myocardial infarction and more than 50% of intrahospital mortality. There are no specific guidelines for the management of acute coronary syndromes (ACS) in the elderly. SETTING: Although antithrombotic therapy seems to be effective and safe in such patients, it requires specific precautions and treatment adjustments because of the higher bleeding risk due to comorbidities such as renal function impairment and malnutrition. RESULTS: Scientific evidence concerning elderly patients is scarce as they are either excluded or underrepresented in most randomized trials. Overall, the antithrombotic therapy needs to be adapted to avoid complications, mainly bleeding complications, without compromising the effectiveness of the treatment in this high-risk population. CONCLUSION: In the present paper, we review the current treatment strategies in ACS while focusing on data concerning the elderly, according to available data in pivotal trials and in both AHA/ACC and ESC guidelines.

Assessment of endothelial function and myocardial flow reserve using (15)O-water PET without attenuation correction.

PURPOSE: Myocardial blood flow (MBF) measurement using positron emission tomography (PET) from the washout rate of (15)O-water is theoretically independent of tissue attenuation. The aim of this study was to evaluate the impact of not using attenuation correction in the assessment of coronary endothelial function and myocardial flow reserve (MFR) using (15)O-water PET. METHODS: We retrospectively processed 70 consecutive (15)O-water PET examinations obtained at rest and during cold pressor testing (CPT) in patients with dilated cardiomyopathy (n = 58), or at rest and during adenosine infusion in heart transplant recipients (n = 12). Data were reconstructed with attenuation correction (AC) and without attenuation correction (NAC) using filtered backprojection, and MBF was quantified using a single compartmental model. The agreement between AC and NAC data was assessed using Lin's concordance correlation coefficient followed by Bland-Altman plot analysis. RESULTS: Regarding endothelial function, NAC PET showed poor reproducibility and poor agreement with AC PET data. Conversely, NAC PET demonstrated high reproducibility and a strong agreement with AC PET for the assessment of MFR. CONCLUSION: Non-attenuation-corrected (15)O-water PET provided an accurate measurement of MFR compared to attenuation-corrected PET. However, non-attenuation-corrected PET data were less effective for the assessment of endothelial function using CPT in this population.

Prehospital fibrinolysis versus primary percutaneous coronary intervention in ST-elevation myocardial infarction: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion strategy in patients with ST-elevation myocardial infarction (STEMI), but its benefit over prehospital fibrinolysis (FL) is not clear. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials in which outcomes of patients with STEMI managed with FL early in the prehospital setting versus PPCI were compared. RESULTS: Compared with PPCI, FL was consistently associated with similar rates of short-term (30-90 days) death (relative risk [RR] 0.94, 95 % CI 0.67-1.31) and cardiovascular death (RR 0.95, 95 % CI 0.64-1.4), a decreased risk of cardiogenic shock (RR 0.67, 95 % CI 0.48-0.95), and an increased risk of any stroke (RR 3.57, 95 % CI 1.39-9.17) and hemorrhagic stroke (RR 4.37, 95 % CI 1.25-15.26). FL was also associated with similar rates of 1-year mortality (RR 1.01, 95 % CI 0.75-1.34) and major bleeding (RR 1.31, 95 % CI 0.96-1.78) in comparison with PPCI, but with a notable level (I 2 index 30.5 % and 59.8 %) of heterogeneity among studies. CONCLUSIONS: Our study suggests that, compared with PPCI, FL performed in the early prehospital setting is associated with similar mortality rates, lower rates of cardiogenic shock, and higher rates of stroke in patients with STEMI. Although the number of studies comparing the two strategies is relatively low, our results support prehospital FL and transfer to hub percutaneous coronary intervention (PCI) centers as a valid alternative to PPCI, allowing potential limitation of resources allocated to developing proximity 24/7 PCI facilities.

First determination of the heart-to-mediastinum ratio using cardiac dual isotope (¹²³I-MIBG/99mTc-tetrofosmin) CZT imaging in patients with heart failure: the ADRECARD study.

PURPOSE: Cardiac innervation is assessed using the heart-to-mediastinum ratio (HMR) of metaiodobenzylguanidine (MIBG) on planar imaging using Anger single photon emission computed tomography (A-SPECT). The aim of the study was to determine the HMR of MIBG obtained using a CZT-based camera (D-SPECT; Spectrum Dynamics, Israel) in comparison with that obtained using conventional planar imaging. METHODS: The ADRECARD study prospectively evaluated 44 patients with heart failure. They underwent planar acquisition using the A-SPECT camera 4 h after (123)I-MIBG injection (236.4 ± 39.7 MBq). To localize the heart using D-SPECT, (99m)Tc-tetrofosmin (753 ± 133 MBq) was administered and dual isotope acquisition was performed using the D-SPECT system. HMR was calculated using both planar A-SPECT imaging and front view D-SPECT cine data. In a phantom study, we estimated a model fitting the A-SPECT and the D-SPECT data that was further applied to correct for differences between the cameras. RESULTS: A total of 44 patients (39 men and 5 women, aged 60 ± 11 years) with ischaemic (31 patients) and nonischaemic (13 patients) cardiomyopathy completed the study. Most patients (28 of 44) were NYHA class II, and the mean left ventricular ejection fraction was 33 ± 7 %. The mean HMR values were 1.34 ± 0.15 and 1.45 ± 0.27 from A-SPECT and D-SPECT, respectively (p < 0.0001). After correction, Lin's concordance correlation showed an almost perfect concordance between corrected D-SPECT HMR and A-SPECT HMR, and Bland-Altman analysis demonstrated a high agreement between the two measurements. CONCLUSION: The ADRECARD study demonstrated that determination of late HMR during cardiac MIBG imaging using dual isotope ((123)I and (99m)Tc) acquisition on a CZT camera (D-SPECT) is feasible in patients with heart failure. A linear correction based on the phantom study yielded a high agreement between (123)I MIBG HMR obtained using a CZT camera and that from conventional planar imaging.

Segmental and global left ventricular function assessment using gated SPECT with a semiconductor Cadmium Zinc Telluride (CZT) camera: phantom study and clinical validation vs cardiac magnetic resonance.

BACKGROUND: We evaluated gated-SPECT using a Cadmium-Zinc-Telluride (CZT) camera for assessing global and regional left ventricular (LV) function. METHODS: A phantom study evaluated the accuracy of wall thickening assessment using systolic count increase on both Anger and CZT (Discovery 530NMc) cameras. The refillable phantom simulated variable myocardial wall thicknesses. The apparent count increase (%CI) was compared to the thickness increase (%Th). CZT gated-SPECT was compared to cardiac magnetic resonance (CMR) in 27 patients. Global and regional LV function (wall thickening and motion) were quantified and compared between SPECT and CMR data. RESULTS: In the phantom study using a 5-mm object, the regression between %CI and %Th was significantly closer to the line of identity (y = x) with the CZT (R (2) = 0.9955) than the Anger (R (2) = 0.9995, P = .03). There was a weaker correlation for larger objects (P = .003). In patients, there was a high concordance between CZT and CMR for ESV, EDV, and LVEF (all CCC >0.80, P < .001). CZT underestimated %CI and wall motion (WM) compared to CMR (P < .001). The agreement to CMR was better for WM than wall thickening. CONCLUSION: The Discovery 530NMc provided accurate measurements of global LV function but underestimated regional wall thickening, especially in patients with increased wall thickness.

Atorvastatin-induced cardioprotection of human myocardium is mediated by the inhibition of mitochondrial permeability transition pore opening via tumor necrosis factor-α and Janus kinase/signal transducers and activators of transcription pathway.

BACKGROUND: The role of tumor necrosis factor-α (TNF-α), Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, and mitochondrial Permeability Transition Pore in atorvastatin-induced cardioprotection were examined in human myocardium, in vitro. METHODS: Isometric force of contraction of human right atrial trabeculae was recorded during 30-min hypoxia and 60-min reoxygenation (control) and in the presence of atorvastatin (0.1 µM, 1 µM, 10 µM). In early reoxygenation, the TNF-α inhibitor, AG490 (inhibitor of JAK/STAT), or atractyloside (mitochondrial Permeability Transition Pore opener), were administered. Cyclosporine A (inhibitor of mitochondrial Permeability Transition Pore opening) was administered during the first minute of reoxygenation alone or in presence of atorvastatin and TNF-α inhibitor or AG490. The force of contraction (percentage of baseline) at the end of reoxygenation period was compared (mean ± SD; n = 6 in each group). Protein expression of JAK/STAT pathway was measured using Western immunoblotting. RESULTS: Atorvastatin 0.1 µM (70 ± 9%), 1 µM (85 ± 5%), 10 µM (89 ± 5%), and Cyclosporine A (87 ± 10%) improved the recovery of force of contraction at the end of reoxygenation, as compared with control (50 ± 3%). Atorvastatin 1 µM (4.64 ± 2.90 ng · ml(-1) · g(-1) of tissue) decreased the release of troponin Ic after hypoxia-reoxygenation (control: 26.34 ± 19.30 ng · ml(-1) · g(-1); P < 0.001). The enhanced recovery of force of contraction after atorvastatin administration was abolished by TNF-α inhibitor (53 ± 8%), AG490 (56 ± 7%), atractyloside (48 ± 8%). Cyclosporine A restored the atorvastatin-induced cardioprotection abolished by TNF-α inhibitor (87 ± 6%) and AG490 (83 ± 9%). Atorvastatin significantly increased the phosphorylation of JAK-2 and STAT-3, TNF-α inhibitor abolished the enhanced phosphorylation of JAK-2 and STAT-3 by atorvastatin. CONCLUSIONS: Atorvastatin-induced cardioprotection involved the inhibition of the mitochondrial Permeability Transition Pore opening via the activation of TNF-α and the JAK/STAT pathway in early reoxygenation.

CRT-D replacement strategy: results of the BioCONTINUE study.

BACKGROUND: In patients with cardiac resynchronization therapy defibrillators (CRT-Ds), the need for implantable cardioverter-defibrillator (ICD) back-up may be questionable at time of CRT-D replacement (REP) if ICD implant criteria are no longer met due to an improved left ventricular ejection fraction (LVEF) and if no major ventricular arrhythmic event (VAE) occurred during the CRT-D lifetime. The aim of our study was to assess the relevance of ICD back-up and predictors of VAE after REP in primary prevention CRT-D patients. METHODS: The prospective, observational, international BioCONTINUE study investigated the rate of patients with at least 1 sustained VAE (sVAE) post-REP and searched for predictive factors of sVAE. RESULTS: Two hundred seventy-six patients (70 ± 10 years, 77% men, mean LVEF 40.6 ± 12.6%) were followed for 28.4 ± 10.2 months. The rate of patients with sVAE was 8.3%, 10.3%, and 21.2% at 1, 2, and 4 years post-REP. Patients without persistent ICD indication at REP still had a sVAE rate of 5.7% (95% CI 2.3-11.5%) at 2 years. In multivariate analysis, predictive factors of subsequent sVAE were (i) persistent ICD indication (hazard ratio (HR) 3.6; 95% CI 1.6-8.3; p = 0.003); (ii) 64-72 years of age as compared to ≥ 79 years (HR 3.7; 95% CI 1.4-9.7; p = 0.008); and (iii) ischemic heart disease (HR 4.4; 95% CI 2.1-9.3; p < 0.0001). CONCLUSIONS: The risk of sVAE (21.2% at 4 years post-REP) depends on age, ischemic heart disease, and ICD indication at the time of REP. A non-trivial risk of sVAE remains in patients without persistent ICD indication. CLINICAL TRIAL REGISTRATION: NCT02323503.

Atrial Fibrillation Incidence Associated With Exposure to Anticancer Drugs Used as Monotherapy in Clinical Trials.

Background: The incidence of atrial fibrillation (AF) associated with anticancer drugs in cancer patients remains incompletely defined. Objectives: The primary outcome was the annualized incidence rate of AF reporting associated with exposure to 1 of 19 anticancer drugs used as monotherapy in clinical trials. The authors also report the annualized incidence rate of AF reported in the placebo arms of these trials. Methods: The authors systematically searched ClinicalTrials.gov for phase 2 and 3 cancer trials studying 19 different anticancer drugs of interest used as monotherapy, up to September 18, 2020. The authors performed a random-effects meta-analysis to compute summary AF annualized incidence rate with its 95% CI using log transformation and inverse variance weighting. Results: A total of 191 clinical trials (47.1% were randomized) of 16 anticancer drugs across 26,604 patients were included. Incidence rates could be calculated for 15 drugs administered singly as monotherapy. Summary annualized incidence rates of AF reporting associated with exposure to 1 of the 15 anticancer drugs used as monotherapy were derived; these ranged from 0.26 to 4.92 per 100 person-years. The 3 highest annualized incidence rates of AF reporting were found for ibrutinib 4.92 (95% CI: 2.91-8.31), clofarabine 2.38 (95% CI: 0.66-8.55), and ponatinib 2.35 (95% CI: 1.78-3.12) per 100 person-years. Summary annualized incidence rate of AF reporting in the placebo arms was 0.25 per 100 person-years (95% CI: 0.10-0.65). Conclusions: AF reporting is not a rare event associated with anticancer drugs in clinical trials. A systematic and standardized AF detection should be considered in oncological trials, particularly those studying anticancer drugs associated with high AF rates. (Incidence of atrial fibrillation associated with anticancer drugs exposure in monotherapy, A safety meta-analysis of phase 2 and 3 clinical trials; CRD42020223710).