ABSTRACT
BACKGROUND: Sleep-disordered breathing (SDB) is a common comorbidity in patients with heart failure (HF) and is associated with worse prognosis. OBJECTIVES: This study evaluated the effects of adaptive servo-ventilation (ASV) on morbidity and mortality in a large heterogeneous population of HF patients with different etiologies/phenotypes. METHODS: Consecutive HF patients with predominant central sleep apnea (± obstructive sleep apnea) indicated for ASV were included; the control group included patients who refused or stopped ASV before three months follow-up. Six homogenous clusters were determined using the latent class analysis (LCA) method. The primary endpoint was time to composite first event (all-cause death, lifesaving cardiovascular intervention, or unplanned hospitalization for worsening of chronic HF). RESULTS: Of 503 patients at baseline, 324 underwent 2-year follow-up. Compared to control group, 2-year primary endpoint event-free survival was significantly greater in patients in ASV group only in univariable analysis (1.67, 95% [1.12-2.49]; p = 0.01). Secondary endpoints, event-free of cardiovascular death or heart failure-related hospitalization and all-cause death or all-cause hospitalization were positively impacted by ASV (univariate and multivariable analysis). LCA identified two groups, with preserved and mid-range left ventricular ejection fraction (LVEF) and severe hypoxia, in whom ASV increase prognosis benefit. CONCLUSIONS: Patients with HF and SDB are a highly heterogeneous group identified using LCA. Systematic deep phenotyping is essential to ensure that ASV is prescribed to those benefit from therapy, as ASV use in patients with severe hypoxic burden and those with HFpEF was associated with a significant reduction in cardiovascular events and mortality. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01831128.
Subject(s)
Heart Failure , Sleep Apnea Syndromes , Sleep Apnea, Central , Humans , Heart Failure/complications , Heart Failure/therapy , Stroke Volume , Follow-Up Studies , Ventricular Function, Left , Sleep Apnea Syndromes/complications , Sleep Apnea Syndromes/therapy , Sleep Apnea, Central/complications , Chronic Disease , Treatment OutcomeABSTRACT
RATIONALE: Adaptive servo ventilation (ASV) is contraindicated in patients with systolic heart failure (HF) who have a left ventricular ejection fraction (LVEF) below 45% and predominant central sleep apnoea (CSA). However, the effects of ASV in other HF subgroups have not been clearly defined. OBJECTIVE: The European, multicentre, prospective, observational cohort trial, FACE, evaluated the effects of ASV therapy on morbidity and mortality in patients with HF with sleep-disordered breathing (SDB); 3-month outcomes in patient subgroups defined using latent class analysis (LCA) are presented. METHODS: Consecutive patients with HF with predominant CSA (±obstructive sleep apnoea) indicated for ASV were included from 2009 to 2018; the non-ASV group included patients who refused/were noncompliant with ASV. The primary endpoint was time to composite first event (all-cause death, lifesaving cardiovascular intervention or unplanned hospitalisation for worsening of chronic HF). MEASUREMENTS AND MAIN RESULTS: Baseline assessments were performed in 503 patients, and 482 underwent 3-month follow-up. LCA identified six discrete patient clusters characterised by variations in LVEF, SDB type, age, comorbidities and ASV acceptance. The 3- month rate of primary outcome events was significantly higher in cluster 1 patients (predominantly men, low LVEF, severe HF, CSA; 13.9% vs 1.5%-5% in other clusters, p<0.01). CONCLUSION: For the first time, our data identified homogeneous patient clusters representing clinically relevant subgroups relating to SDB management in patients with HF with different ASV usage, each with a different prognosis. This may improve patient phenotyping in clinical practice and allow individualisation of therapy.
Subject(s)
Heart Failure , Sleep Apnea Syndromes , Heart Failure/complications , Heart Failure/therapy , Humans , Male , Prospective Studies , Sleep Apnea Syndromes/therapy , Stroke Volume , Treatment Outcome , Ventricular Function, LeftABSTRACT
Background and Purpose: The objective of the study was to assess the effectiveness of individual direct oral anticoagulants versus vitamin K antagonists for primary prevention of stroke (ischemic and hemorrhagic) in routine clinical practice in patients with various clinical risk factors depending on their atrial fibrillation (AF) patterns. Methods: A nested case-referent study was conducted using data from 2 national registries of patients with stroke and AF. Stroke cases with previous history of AF were matched to up to 2 randomly selected referent patients with AF and no stroke. The association of individual anticoagulant use with ischemic or hemorrhagic stroke was studied in patients with or without permanent AF using multivariable conditional logistic models, controlled for clinically significant risk factors and multiple other cardiovascular risk factors. Results: In total, 2586 stroke cases with previous AF and 4810 nonstroke referent patients with AF were retained for the study. Direct oral anticoagulant users had lower odds of stroke of any type than vitamin K antagonist users: the adjusted-matched OR for ischemic stroke were 0.70 (95% CI, 0.500.98) for dabigatran, 0.68 (95% CI, 0.530.86) for rivaroxaban, and 0.73 (95% CI, 0.521.02) for apixaban while for hemorrhagic stroke they were 0.31 (95% CI, 0.140.68), 0.64 (95% CI, 0.391.06), and 0.70 (95% CI, 0.331.49), respectively. The effects of individual direct oral anticoagulants relative to vitamin K antagonists were similar in permanent AF and nonpermanent AF patients. Conclusions: Similar results were observed for each direct oral anticoagulant in real life as those observed in the pivotal clinical trials. The pattern of AF did not affect the outcome.
Subject(s)
Anticoagulants/therapeutic use , Atrial Fibrillation/drug therapy , Stroke/prevention & control , Administration, Oral , Aged , Aged, 80 and over , Atrial Fibrillation/complications , Case-Control Studies , Dabigatran/therapeutic use , Female , Heart Disease Risk Factors , Humans , Intracranial Hemorrhages/complications , Intracranial Hemorrhages/prevention & control , Ischemic Stroke/prevention & control , Male , Middle Aged , Risk Factors , Treatment Outcome , Vitamin K/antagonists & inhibitorsABSTRACT
PURPOSE: FACE is a prospective cohort study designed to assess the effect of adding adaptive servoventilation (ASV) to standard care on morbidity and mortality in patients with chronic heart failure (HF) with preserved (HFpEF), mid-range (HFmrEF) or reduced ejection fraction (HFrEF) who have sleep-disordered breathing (SDB) with an indication for ASV. We describe the study design, ongoing data collection and baseline participant characteristics. PARTICIPANTS: Consecutive patients with HFpEF, HFmrEF or HFrEF plus SDB with central sleep apnoea (CSA) and indication for ASV were enrolled in the study cohort between November 2009 and December 2018; the ASV group includes those treated with ASV and the control group consists of patients who refused ASV or stopped treatment early. Follow-up is based on standard clinical practice, with visits at inclusion, after 3, 12 and 24 months of follow-up. Primary endpoint is the time to first event: all-cause death or unplanned hospitalisation (or unplanned prolongation of a planned hospitalisation) for worsening of HF, cardiovascular death or unplanned hospitalisation for worsening of HF, and all-cause death or all-cause unplanned hospitalisation. FINDINGS TO DATE: 503 patients have been enrolled, mean age of 72 years, 88% male, 31% with HFrEF. HF was commonly of ischaemic origin, and the number of comorbidities was high. SDB was severe (median Apnoea-Hypopnoea Index 42/hour), and CSA was the main indication for ASV (69%). HF was highly symptomatic; most patients were in NYHA class II (38%) or III (29%). FUTURE PLANS: Patient follow-up is ongoing. Given the heterogeneous nature of the enrolled population, a decision was made to use latent class analysis to define homogeneous patient subgroups, and then evaluate outcomes by cluster, and in the ASV and control groups (overall and within patient clusters). First analysis will be performed after 3 months, a second analysis at the 2-year follow-up. TRIAL REGISTRATION NUMBER: NCT01831128; Pre-results.
Subject(s)
Heart Failure , Sleep Apnea Syndromes , Aged , Female , Follow-Up Studies , Heart Failure/complications , Heart Failure/therapy , Humans , Male , Middle Aged , Prospective Studies , Sleep Apnea Syndromes/epidemiology , Sleep Apnea Syndromes/therapy , Stroke Volume , Ventricular Function, LeftABSTRACT
BACKGROUND: Although the implantable cardioverter-defibrillator (ICD) remains the main therapy for Brugada syndrome (BrS), it does not reduce life-threatening ventricular arrhythmia. Based on pathophysiologic mechanisms, hydroquinidine (HQ) has been suggested for effective prevention of arrhythmia. OBJECTIVE: The purpose of this study was to provide evidence-based data supporting HQ use to prevent life-threatening ventricular arrhythmia in high-risk patients with BrS. METHODS: We performed a prospective multicenter randomized (HQ vs placebo) double-blind study with two 18-month crossover phases in patients with BrS and implanted with an ICD. RESULTS: Among the 50 patients enrolled (mean age 47.0 ± 11.4 years, 42 [84%] male), 26 (52%) fully completed both phases. Thirty-four (68%) presented HQ-related side effects, mainly gastrointestinal, which led to discontinuation of the therapy in 13 (26%). HQ lengthened the QTc interval (409 ± 32 ms vs 433 ± 37 ms; P = .027) and increased repolarization dispersion as evaluated by Tpe max in precordial leads (89 ± 15 ms vs 108 ± 27 ms; P <.0001) with no significant changes in J-point elevation. During the 36-month follow-up, 1 appropriate ICD shock (0.97% event per year), 1 self-terminating ventricular fibrillation, and 1 inappropriate ICD shock occurred under placebo therapy. No arrhythmic events were reported under HQ therapy. CONCLUSION: Although HQ seems to be effective in preventing life-threatening ventricular arrhythmia, it could not be an alternative for ICD implantation. Its frequent side effects greatly reduce its probable compliance and therefore do not reveal a significant effect. HQ increases repolarization dispersal with no changes in BrS pattern, which could indicate a more complex action of HQ than its Ito blocking effect alone.
Subject(s)
Brugada Syndrome/therapy , Defibrillators, Implantable , Electrocardiography , Quinidine/analogs & derivatives , Ventricular Fibrillation/prevention & control , Adult , Anti-Arrhythmia Agents/therapeutic use , Brugada Syndrome/complications , Brugada Syndrome/physiopathology , Cross-Over Studies , Double-Blind Method , Female , Follow-Up Studies , Heart Rate/drug effects , Humans , Male , Middle Aged , Prospective Studies , Quinidine/therapeutic use , Risk Factors , Time Factors , Ventricular Fibrillation/etiology , Ventricular Fibrillation/physiopathologyABSTRACT
Natriuretic peptides (BNP and NT-proBNP) are recognized as gold-standard predictive markers in Heart Failure (HF). However, currently ST2 (member of the interleukin 1 receptor family) has emerged as marker of inflammation, fibrosis and cardiac stress. We evaluated ST2 and CRP as prognostic markers in 178 patients with chronic heart failure in comparison with other classical markers such as clinical established parameters but also biological markers: NT-proBNP, hs-cTnT alone or in combination. In multivariate analysis, subsequent addition of ST2 led to age, CRP and ST2 as the only remaining predictors of all-cause mortality (HR 1.03, HR 1.61 and HR 2.75, respectively) as well as of cardiovascular mortality (HR 1.00, HR 2.27 and HR 3.78, respectively). The combined increase of ST2 and CRP was significant for predicting worsened outcomes leading to identify a high risk subgroup that individual assessment of either marker. The same analysis was performed with ST2 in combination with Barcelona score. Overall, our findings extend previous data demonstrating that ST2 in combination with CRP as a valuable tool for identifying patients at risk of death.
Subject(s)
Biomarkers/blood , C-Reactive Protein/metabolism , Heart Failure/blood , Interleukin-1 Receptor-Like 1 Protein/blood , Aged , Female , Heart Failure/mortality , Humans , Male , Middle Aged , Multivariate Analysis , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Prognosis , Risk AssessmentABSTRACT
The programming of implantable cardioverter-defibrillators (ICDs) influences inappropriate shock rates. The aim of the study is to analyse rates of patients with appropriate and inappropriate shocks according to detection zones in the OPTION trial. All patients received dual chamber (DC) ICDs randomly assigned to be programmed either to single chamber (SC) or to DC settings including PARAD+ algorithm. In a post-hoc analysis, rates of patients with inappropriate and appropriate shocks were calculated for shocks triggered at heart rates ≥ 170 bpm (ventricular tachycardia zone) and at rates ≥ 200 bpm (ventricular fibrillation zone). In the SC group, higher rates of patients with total and inappropriate shocks were delivered at heart rates ≥ 170 bpm than at rates ≥ 200 bpm (total shocks: 21.1% vs. 16.6%; p = 0.002; inappropriate shocks: 7.6% vs. 4.5%, p = 0.016; appropriate shocks: 15.2% vs. 13.5%; p = n.s.). No such differences were observed in the DC group (total shocks: 14.3% vs. 12.6%; p = n.s.; inappropriate shocks: 3.9% vs. 3.6%; p = n.s.; appropriate shocks: 12.2% vs. 10.4%; p = n.s.). The higher frequency of patients with total shocks with SC settings than with DC settings that benefit from PARAD+ was driven by a higher percentage of patients with inappropriate shocks in the VT zone (170-200 bpm) in the SC population.
Subject(s)
Defibrillators, Implantable , Electric Countershock/instrumentation , Electric Countershock/methods , Tachycardia, Ventricular/therapy , Aged , Algorithms , Death, Sudden, Cardiac , Female , Heart Rate , Humans , Male , Middle Aged , Prospective Studies , Software , Treatment OutcomeABSTRACT
BACKGROUND: Risk stratification in Brugada syndrome (BS) remains controversial. The time interval between the peak and the end of the T wave (Tpe interval), a marker of transmural dispersion of repolarization, has been linked to malignant ventricular arrhythmias in various settings but leads to discordant results in BS. OBJECTIVE: We study the correlation of the Tpe interval with arrhythmic events in a large cohort of patients with BS. METHODS: A total of 325 consecutive patients with BS (mean age 47±13 years, 259 men-80%) with spontaneous (n=143, 44%) or drug-induced (n=182, 56%) type 1 electrocardiogram were retrospectively included. 235 were asymptomatic (70%), 80 presented with unexplained syncope (22%), and 10 presented with sudden death (SD) or appropriate implantable cardioverter-defibrillator therapy (AT) (8%) at diagnosis or over a mean follow-up of 48 ± 34 months. The Tpe interval was calculated as the difference between the QT interval and the QT peak interval as measured in each of the precordial leads. RESULTS: The Tpe interval from lead V1 to lead V4, maximum value of the Tpe interval (max Tpe), and Tpe dispersion in all precordial leads were significantly higher in patients with SD/AT or in patients with syncope than in asymptomatic patients (P < .001). A max Tpe of ≥100 ms was present in 47 of 226 asymptomatic patients (21%), in 48 of 73 patients with syncope (66%), and in 22 of 26 patients with SD/AT (85%) (P < .0001). In multivariate analysis, a max Tpe of ≥100 ms was independently related to arrhythmic events (odds ratio 9.61; 95% confidence interval 3.13-29.41; P < .0001). CONCLUSION: The Tpe interval in the precordial leads is highly related to malignant ventricular arrhythmias in this large cohort of patients with BS. This simple electrocardiographic parameter could be used to refine risk stratification.
Subject(s)
Brugada Syndrome/complications , Brugada Syndrome/physiopathology , Electrocardiography , Adult , Brugada Syndrome/therapy , Defibrillators, Implantable , Female , Humans , Male , Middle Aged , Predictive Value of Tests , ROC Curve , Retrospective Studies , Risk AssessmentABSTRACT
OBJECTIVES: The OPTION (Optimal Anti-Tachycardia Therapy in Implantable Cardioverter-Defibrillator Patients Without Pacing Indications) trial sought to compare long-term rates of inappropriate shocks, mortality, and morbidity between dual-chamber and single-chamber settings in implantable cardioverter-defibrillators (ICDs) patients. BACKGROUND: The use of dual-chamber ICDs potentially allows better discrimination of supraventricular arrhythmias and thereby reduces inappropriate shocks. However, it may lead to detrimental ventricular pacing. METHODS: This prospective multicenter, single-blinded trial enrolled 462 patients with de novo primary or secondary prevention indications for ICD placement and with left ventricular ejection fractions ≤40% despite optimal tolerated pharmacotherapy. All patients received atrial leads and dual-chamber defibrillators that were randomized to be programmed either with dual-chamber or single-chamber settings. In the dual-chamber setting arm, the PARAD+ algorithm, which differentiates supraventricular from ventricular arrhythmias, and SafeR mode, to minimize ventricular pacing, were activated. In the single-chamber setting arm, the acceleration, stability, and long cycle search discrimination criteria were activated, and pacing was set to VVI 40 beats/min. Ventricular tachycardia detection was required at rates between 170 and 200 beats/min, and ventricular fibrillation detection was activated above 200 beats/min. RESULTS: During a follow-up period of 27 months, the time to the first inappropriate shock was significantly longer in the dual-chamber setting arm (p = 0.012, log-rank test), and 4.3% of patients in the dual-chamber setting group compared with 10.3% in the single-chamber setting group experienced inappropriate shocks (p = 0.015). Rates of all-cause death or cardiovascular hospitalization were 20% for the dual-chamber setting group and 22.4% for the single-chamber setting group and satisfied the pre-defined margin for equivalence (p < 0.001). CONCLUSIONS: Therapy with dual-chamber settings for ICD discrimination combined with algorithms for minimizing ventricular pacing was associated with reduced risk for inappropriate shock compared with single-chamber settings, without increases in mortality and morbidity. (Optimal Anti-Tachycardia Therapy in Implantable Cardioverter-Defibrillator [ICD] Patients Without Pacing Indications [OPTION]; NCT00729703).
Subject(s)
Atrial Fibrillation/therapy , Defibrillators, Implantable/adverse effects , Tachycardia, Supraventricular/therapy , Atrial Fibrillation/mortality , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prospective Studies , Prosthesis Design , Single-Blind Method , Tachycardia, Supraventricular/mortality , Treatment OutcomeABSTRACT
BACKGROUND: Both type 1 myotonic dystrophy (MD1) and Brugada syndrome (BrS) may be complicated by conduction disturbances and sudden death. Spontaneous BrS has been observed in MD1 patients, but the prevalence of drug-induced BrS in MD1 is unknown. OBJECTIVE: The purpose of this study was to prospectively assess the prevalence of type 1 ST elevation as elicited during pharmacologic challenge with Class 1C drugs in a subgroup of MD1 patients and to further establish correlations with ECG and electrophysiologic variables and prognosis. METHODS: From a group of unselected 270 MD1 patients, ajmaline or flecainide drug challenge was performed in a subgroup of 44 patients (27 men, median age 43 years) with minor depolarization/repolarization abnormalities suggestive of possible BrS. The presence of type 1 ST elevation after drug challenge was correlated to clinical, ECG, and electrophysiologic variables. RESULTS: Eight of 44 patients (18%) presented with BrS after drug challenge. BrS was seen more often in men (26% vs 6%, P = .09) and was related to younger age (35 vs 48 years, P = .07). BrS was not correlated to symptoms, baseline ECG, HV interval, results of signal-averaged ECG, or abnormalities on ambulatory recordings. MD1 patients with BrS had longer corrected QT intervals, greater increase in PR interval after drug challenge, and higher rate of inducible ventricular arrhythmias (62% vs 21%, P = .03). Twelve patients were implanted with a pacemaker and 5 with an implantable cardioverter-defibrillator. Significant bradycardia did not occur in any patients, and malignant ventricular arrhythmia never occurred during median 7-year follow-up (except 1 hypokalemia-related ventricular fibrillation). CONCLUSION: BrS is elicited by a Class 1 drug in 18% of MD1 patients presenting with minor depolarization/repolarization abnormalities at baseline, but the finding seems to be devoid of a prognostic role.
Subject(s)
Ajmaline/adverse effects , Brugada Syndrome/chemically induced , Death, Sudden, Cardiac/epidemiology , Electrocardiography/drug effects , Flecainide/adverse effects , Myotonic Dystrophy/drug therapy , Adult , Ajmaline/therapeutic use , Brugada Syndrome/epidemiology , Brugada Syndrome/physiopathology , Death, Sudden, Cardiac/etiology , Defibrillators, Implantable , Female , Flecainide/therapeutic use , Follow-Up Studies , France/epidemiology , Humans , Incidence , Male , Myotonic Dystrophy/complications , Myotonic Dystrophy/physiopathology , Prevalence , Prognosis , Prospective Studies , Survival Rate/trends , Voltage-Gated Sodium Channel BlockersSubject(s)
Continuous Positive Airway Pressure/methods , Heart Failure/diagnosis , Heart Failure/therapy , Hemodynamics/physiology , Severity of Illness Index , Adult , Aged , Cardiac Output/physiology , Chronic Disease , Female , Heart Failure/physiopathology , Humans , Male , Middle Aged , Treatment OutcomeABSTRACT
Prevalence and prognostic value of conduction disturbances in patients with the Brugada syndrome (BrS) remains poorly known. Electrocardiograms (ECGs) from 325 patients with BrS (47 ± 13 years, 258 men) with spontaneous (n = 143) or drug-induced (n = 182) type 1 ECG were retrospectively reviewed. Two hundred twenty-six patients (70%) were asymptomatic, 73 patients (22%) presented with unexplained syncope, and 26 patients (8%) presented with sudden death or implantable cardioverter-defibrillator appropriated therapies at diagnosis or during a mean follow-up of 48 ± 34 months. P-wave duration of ≥120 ms was present in 129 patients (40%), first degree atrioventricular block (AVB) in 113 (35%), right bundle branch block (BBB) in 90 (28%), and fascicular block in 52 (16%). Increased P-wave duration, first degree AVB, and right BBB were more often present in patients after drug challenge than in patients with spontaneous type 1 ST elevation. Left BBB was present in 3 patients. SCN5A mutation carriers had longer P-wave duration and longer PR and HV intervals. In multivariate analysis, first degree AVB was independently associated with sudden death or implantable cardioverter-defibrillator appropriated therapies (odds ratio 2.41, 95% confidence interval 1.01 to 5.73, p = 0.046) together with the presence of syncope and spontaneous type 1 ST elevation. In conclusion, conduction disturbances are frequent and sometimes diffuse in patients with BrS. First degree AVB is independently linked to outcome and may be proposed to be used for individual risk stratification.
Subject(s)
Brugada Syndrome/epidemiology , Electrocardiography , Heart Conduction System/physiology , Brugada Syndrome/complications , Brugada Syndrome/physiopathology , Confidence Intervals , Death, Sudden, Cardiac/epidemiology , Death, Sudden, Cardiac/etiology , Female , Follow-Up Studies , France/epidemiology , Humans , Male , Middle Aged , Odds Ratio , Prevalence , Prognosis , Retrospective Studies , Survival Rate/trendsABSTRACT
Rest is usually recommended in acute pericarditis and acute myocarditis. Given that myocarditis often leads to hospitalization, this task seems easy to carry out in hospital practice; however, it could be a real challenge at home in daily life. Heart rate-lowering treatments (mainly beta-blockers) are usually recommended in case of acute myocarditis, especially in case of heart failure or arrhythmias, but level of proof remains weak. Calcium channel inhibitors and digoxin are sometimes proposed, albeit in limited situations. It is possible that rest or even heart rate-lowering treatments could help to manage these patients by preventing heart failure as well as by limiting "mechanical inflammation" and controlling arrhythmias, especially life-threatening ones. Whether heart rate has an effect on inflammation remains unclear. Several questions remain unsolved, such as the duration of such treatments, especially in light of new heart rate-lowering treatments, such as ivabradine. In this review, we discuss rest and heart-rate lowering medications for the treatment of pericarditis and myocarditis. We also highlight some work in experimental models that indicates the beneficial effects of such treatments for these conditions. Finally, we suggest certain experimental avenues, through the use of animal models and clinical studies, which could lead to improved management of these patients.
Subject(s)
Anti-Arrhythmia Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Heart Rate/drug effects , Myocarditis/drug therapy , Pericarditis/drug therapy , Animals , Humans , Myocarditis/diagnosis , Myocarditis/physiopathology , Pericarditis/diagnosis , Pericarditis/physiopathology , Practice Guidelines as Topic , Treatment OutcomeABSTRACT
BACKGROUND: After synthesis by cardiomyocytes, precursor proBNP1-108 is cleaved into NT-proBNP and BNP. Recently, cross-reactivity between these assays was discussed. The aim of this study was to characterize the cross-reactivities, through a new biochemical innovative approach consisting in the total depletion of the circulating proBNP1-108 in patients with heart failure (HF). METHODS: This prospective study included 180 patients with chronic HF. BNP and NT-proBNP were dosed with commercial kits. ProBNP1-108 was determined using an ELISA research assay specific to the precursor. ProBNP1-108 depletion was performed by immunocapture with a specific antibody targeting exclusively the ProBNP1-108 hinge region. ProBNP1-108, BNP and NT-proBNP levels were determined before and after depletion using this process in HF patients. RESULTS: Mean age was 74.34 +/-12.5 y, and 69% of patients were males. NYHA classes II and III were the most frequent (32% and 45% respectively). Before depletion, ProBNP1-108, NT-proBNP and BNP levels were 316.8+/-265.9 pg/ml; 6,054.0+/-11,539 pg/ml and 684.3+/-82.1 pg/ml respectively, and were closely correlated with NHYA classes. After immuno-depletion, proBNP1-108 was decreased in mean by 96% (p<0.0001), BNP by 53% (p<0.0001) and NT-proBNP by 5%. The relationship between BNP or NT-proBNP and NHYA classes remained unchanged. CONCLUSION: Current BNP and NT-proBNP assays measured as well proBNP molecule. This cross reactivity percentage has been controversial. Thanks to the removal of circulating proBNP1-108 with our immunodepletion process, we are now able to assess the remaining "true" BNP and NT-proBNP molecules and further evaluate their clinical relevance.
Subject(s)
Cross Reactions , Heart Failure/diagnosis , Heart Failure/metabolism , Natriuretic Peptide, Brain/metabolism , Natriuretic Peptide, C-Type/metabolism , Natriuretic Peptides/metabolism , Aged , Aged, 80 and over , Cross Reactions/immunology , Female , Humans , Male , Middle Aged , Natriuretic Peptide, C-Type/immunology , Natriuretic Peptides/immunology , Risk FactorsABSTRACT
Inotropic treatment remains the cornerstone for cardiogenic shock, an emergency that requires immediate resuscitative therapy before shock irreversibly damages vital organs. Although the sympathomimetic drug dobutamine is the most widely-used inotropic drug worldwide, it has several side effects including sinus tachycardia. Dobutamine partly restores systolic heart failure (HF); however, it increases the heart rate (HR) which counterbalances the beneficial effects. Ivabradine, a new selective If inhibitor, provides specific HR reduction and is indicated in stable coronary artery disease and in stable chronic HF with left ventricular dysfunction. Despite scarce data indicating beneficial effects of ivabradine in sinus tachycardia in various clinical settings, this drug remains contraindicated in acute HF. We propose that ivabradine could help to prevent the dobutamine-induced side effects, and that their combination in clinical practice could lead to pure inotropic effects, useful for the management of cardiogenic shock.
Subject(s)
Benzazepines/therapeutic use , Dobutamine/adverse effects , Tachycardia/drug therapy , Humans , Ivabradine , Models, Theoretical , Tachycardia/chemically inducedABSTRACT
Due to the widespread use of anti-inflammatory drugs in clinical practice in various clinical settings and the ease of issue without prescription, many patients are exposed to risks associated to these drugs and particularly to drug interactions. The purpose of this review is to deal with the safety parameters of main anti-inflammatory agents, especially NSAIDs including coxibs, and the different drug interactions with a special emphasis on clinical relevance and recommendations in current practice. We will present consecutively different interactions between anti-inflammatory agents and frequently used drugs. In particular, association between anti-inflammatory drugs and anticoagulants could induce severe complications. Hemorrhagic complications and particularly gastrointestinal bleeding will be discussed together with potential treatment adjustment and likely benefits of new therapies such as specific antagonist of active factor X or II. On the other hand, anti-hypertensive therapies, non specific cytochrome dysregulations and particularly the question of antiarrhythmic drugs, the problem of proton pump inhibitors and specific clinical settings such as drug interactions in elderly are discussed.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anticoagulants/adverse effects , Cardiovascular Diseases/drug therapy , Aged , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anticoagulants/administration & dosage , Anticoagulants/therapeutic use , Clinical Trials as Topic , Drug Interactions , Gastrointestinal Hemorrhage/chemically induced , Humans , Middle Aged , Treatment OutcomeABSTRACT
Anti-inflammatory drugs consist of non-steroidal anti-inflammatory drugs (NSAIDs) including non-selective nsNSAIDs, aspirin, and cyclooxygenase-2 (COX-2)-selective inhibitors also referred to as coxibs, and glucocorticoids (GCs). They are worldwide prescribed drugs for many musculoskeletal conditions, such as osteoarthritis and inflammatory rheumatic diseases. Anti-inflammatory drugs can exert deleterious effects on the cardiovascular system, excluding aspirin. NSAIDs, especially coxibs, have been demonstrated to increase cardiovascular risk and have generated many concerns leading to the reassessment of their benefit/risk ratio. GCs may also induce cardiovascular events, but evidence seems to be less clear. Before prescribing these drugs, an assessment of cardiovascular risk may be judicious. In this review, anti-inflammatory drugs, coxibs, nsNSAIDs and GCs, and the risk of cardiovascular events will be discussed.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Cardiovascular Diseases/epidemiology , Cardiovascular System/drug effects , Glucocorticoids/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Aspirin/adverse effects , Aspirin/pharmacology , Aspirin/therapeutic use , Cardiovascular Diseases/chemically induced , Cardiovascular Diseases/drug therapy , Clinical Trials as Topic , Cyclooxygenase 2 Inhibitors/adverse effects , Cyclooxygenase 2 Inhibitors/pharmacology , Cyclooxygenase 2 Inhibitors/therapeutic use , Glucocorticoids/pharmacology , Glucocorticoids/therapeutic use , Humans , Risk Assessment , Treatment OutcomeABSTRACT
UNLABELLED: PURPOSE AND MEDICAL HYPOTHESIS: Rest is usually recommended in acute pericarditis, as it could help to lower heart rate (HR) and contribute to limit "mechanical inflammation". Whether HR on admission could be correlated and perhaps participate to inflammation has not been reported. METHODS: Between March 2007 and February 2010, we conducted a retrospective study on all patients admitted to our center for acute pericarditis. Diagnosis criteria included two of the following ones: typical chest pain, friction rub, pericardial effusion on cardiac echography, or typical electrocardiogram (ECG) findings. Primary endpoint was biology: CRP on admission, on days 1, 2, 3, and especially peak. RESULTS: We included 73 patients. Median age was 38 years (interquartiles 28-51) and median hospitalization duration was 2.0 days (1.5-3.0). Median heart rate was 88.0 beats per minute (bpm) on admission (interquartiles 76.0-100.0) and 72.0 on discharge (65.0-80.0). Heart rate on admission was significantly correlated with CRP peak (p<0.001), independently of temperature on admission, hospitalization duration and age. Recurrences occurred within 1 month in 32% of patients. Heart rate on hospital discharge was correlated with recurrence, independently of age. CONCLUSION: In acute pericarditis, heart rate on admission is independently correlated with CRP levels and heart rate on discharge seems to be independently correlated to recurrence. This could suggest a link between heart rate and pericardial inflammation.
Subject(s)
Heart Rate/physiology , Models, Cardiovascular , Pericarditis/etiology , Pericarditis/physiopathology , Acute Disease , Adult , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Aspirin/therapeutic use , C-Reactive Protein/metabolism , Female , Humans , Male , Middle Aged , Pericarditis/drug therapy , Retrospective StudiesSubject(s)
Defibrillators, Implantable/adverse effects , Diaphragm/innervation , Electric Countershock/adverse effects , Foreign-Body Migration/etiology , Phrenic Nerve/physiopathology , Aged , Electric Countershock/instrumentation , Electric Stimulation , Foreign-Body Migration/diagnostic imaging , Foreign-Body Migration/physiopathology , Humans , Male , Muscle Contraction , Phrenic Nerve/diagnostic imaging , Prosthesis Design , RadiographyABSTRACT
INTRODUCTION: The study was designed to evaluate the feasibility and performance of right ventricular (RV) mid-septal versus apical implantable defibrillator (ICD) lead placement. METHODS AND RESULTS: SEPTAL is a randomized, noninferiority trial, which randomly assigned patients to implantation of ICD leads in the RV mid-septum versus apex, with a primary objective of comparing the implant success rate of implant at each site, based on strict electrical predefined criteria. We also compared the (1) pacing lead characteristics, (2) rates of appropriate and inappropriate ICD therapies, and (3) all-cause mortality between the 2 sites at 1 year. The trial enrolled 215 patients (mean age = 59.7 ± 12.4 years, mean LVEF = 34.0 ± 14.2%, 84.2% men), of whom 148 (68.8%) presented with ischemic heart disease. The ICD indication was primary prevention in 117 patients (54.4%). The lead was successfully implanted in 96/107 patients (89.7%) assigned to the RV mid-septum, and in 99/108 (91.7%) assigned to the apex (ns). The 1-year rate of lead-related adverse events was similar in both groups. A total of 8 first inappropriate ICD therapies (7.9%) were delivered in the RV mid-septal group, versus 8 (7.8%) in the apical group (ns), while first appropriate therapies were delivered to 22 (21.4%) and 24 patients (23.8%), respectively (ns). All-cause mortality was 7.9% in the RV mid-septal versus 2.9% in the RV apical group (ns). CONCLUSION: This study confirmed the technical feasibility and noninferior performance of ICD leads implanted in the RV mid-septum versus the apex.