Isoproterenol Improves Hemodynamics And Right Ventricle-Pulmonary Artery Coupling After Heart Transplantation.

BACKGROUND: Right ventricular failure (RVF) is a major cause of early mortality after heart transplantation (HT). Isoproterenol has chronotropic, inotropic, and vasodilatory properties which might improve right ventricle function in this setting. We aimed to investigate the hemodynamic effects of isoproterenol on patients with post-HT RVF. METHODS: We conducted a one-year retrospective observational study including patients receiving isoproterenol and dobutamine for early RVF after HT. A comprehensive multiparametric hemodynamic evaluation was performed successively at three times: no isoproterenol, low doses: 0.025 µg/kg/min and high doses: 0.05 µg/kg/min (henceforth respectively called no-iso, low-iso and high-iso). RESULTS: From June 2022 to June 2023, 25 patients, median [IQR25-75] age 54 [38-61] years, were included. Before isoproterenol introduction, all patients received dobutamine and 15 (60%) were on veno-arterial extracorporeal membrane oxygenation. Isoproterenol significantly increased heart rate from 84 [77-99] (no-iso) to 91 [88-106] (low-iso) and 102 [90-122] bpm (high-iso, p<0.001). Similarly, cardiac index raised from 2.3 [1.4-3.1] to 2.7 [1.8-3.4] and 3 [1.9-3.7] l/min/m2 (p<0.001) with concomitant increase of indexed stroke volume (28 [17-34] to 31 [20-34] and 33 [23-35] mL/m2, p<0.05). Effective pulmonary arterial elastance and pressures were not modified by isoproterenol. Pulmonary vascular resistance tended to decrease from 2.9 (1.4-3.6) WU to 2.3 (1.3-3.5) WU, p=0.06. Right ventricular ejection fraction/systolic PAP evaluating RV-PA coupling increased after isoproterenol from 0.8 to 0.9 and 1 %.mmHg-1 (p=0.001). CONCLUSIONS: In post-HT RVF, isoproterenol exhibits chronotropic and inotropic effects, thereby improving RV-PA coupling and resulting in a clinically relevant increase in the cardiac index.

Flecainide to prevent atrial arrhythmia after patent foramen ovale closure, Rationale and design of the randomized AFLOAT study.

INTRODUCTION: Atrial arrhythmia is the most common complication of patent foramen ovale (PFO) closure. The real incidence of post-PFO closure atrial arrhytmia and whether this complication can be prevented is unknown. METHODS/DESIGN: The Assessment of Flecainide to Lower the PFO closure risk of Atrial fibrillation or Tachycardia (AFLOAT) trial is a prospective, national, multicentre, randomized, open-label, superiority trial with a blind evaluation of all the endpoints (PROBE design). A total of 186 patients are randomized in a 1:1:1 ratio immediately after PFO closure to receive Flecainide (150 mg per day in a single sustained-release (SR) dose) for 6 months (Group 1), Flecainide (150 mg per day in a single SR dose) for 3 months (Group 2), or no additional treatment (standard of care) for 6 months (Group 3). The primary endpoint is the percentage of patients with at least one episode of symptomatic or asymptomatic atrial arrhythmia episode (≥30 s) recorded within 3 months after PFO closure on long-term monitoring with an insertable cardiac monitor. Whether 3 months of treatment is sufficient compared to 6 months will be analysed as a secondary objective of the study. CONCLUSION: AFLOAT is the first trial to test the hypothesis that a short treatment with oral Flecainide can prevent the new-onset of atrial arrhythmia after PFO closure. CLINICAL TRIAL REGISTRATION: NCT05213104 (clinicaltrials.gov).

Comparison of three echo-guidance techniques in percutaneous patent foramen ovale closure for stroke prevention: Conventional transoesophageal, microprobe transoesophageal and intracardiac echocardiography.

BACKGROUND: Recent randomized trials have demonstrated a consistent reduction in recurrent stroke after percutaneous transcatheter patent foramen ovale closure versus medical therapy in patients with recent cryptogenic stroke. AIM: To compare the safety and efficacy of intracardiac echocardiography-guided and microprobe transoesophageal echocardiography-guided patent foramen ovale closure under local anaesthesia with transoesophageal echocardiography-guided patent foramen ovale closure under general anaesthesia. METHODS: This prospective observational single-centre study included 194 consecutive patients scheduled for patent foramen ovale closure for secondary prevention of stroke from February 2018 to December 2019. Patients were asked to choose between an intracardiac echocardiography-guided, microprobe transoesophageal echocardiography-guided or transoesophageal echocardiography-guided procedure. The primary endpoint was the rate of successful closure at 6 months, defined as correct positioning of the device without severe shunt on 6-month contrast echocardiography. RESULTS: Successful closure was high and did not differ between groups: 97.8% (95% confidence interval 88.5-99.9%) in the intracardiac echocardiography-guided group versus 96.9% (95% confidence interval 83.8-99.9%) in the microprobe transoesophageal echocardiography-guided group and 99.1% (95% confidence interval 95.3-99.9%) in the transoesophageal echocardiography-guided group (P=0.63). Adverse events related to patent foramen ovale closure were low and did not differ between groups. CONCLUSION: Our preliminary real-world experience suggests good efficacy and safety with intracardiac echocardiography and microprobe transoesophageal echocardiography guidance compared with conventional transoesophageal echocardiography guidance for percutaneous transcatheter patent foramen ovale closure in recurrent stroke prevention.

Implication of the new definition of pulmonary hypertension in patients evaluated for heart transplantation.

BACKGROUND: The 2018 World Symposium on Pulmonary Hypertension (WSPH) changed the definition of pulmonary hypertension (PH) with a new threshold of mean pulmonary artery pressure (mPAP) above 20 mmHg. OBJECTIVE: To evaluate the profile and prognosis of patients with chronic heart failure (HF) considered for heart transplantation with the new definition of PH. METHODS: Patients with chronic HF considered for heart transplantation were classified as mPAP≤20mmHg, mPAP 20-25 mmHg, and mPAP≥25mmHg. Using a multivariate Cox model, we compared the mortality of patients with mPAP20-25mmHg, and mPAP≥25mmHg versus those with mPAP≤20mmHg. RESULTS: Of 693 patients with chronic HF considered for heart transplantation, 12.7%, 77.5% and 9.8% were classified as mPAP20-25mmHg, mPAP≥ 25mmHg and mPAP≤20mmHg. Patients of mPAP ≥ 25mmHg and mPAP 20-25 mmHg categories were older than mPAP ≤ 20 mmHg (56 versus 55 and 52 year-old, p = 0.02) with more frequent co-morbidities. Within 2.8 years, the mPAP20-25mmHg category displayed a higher risk of mortality compared with those of the mPAP≤20mmHg category (aHR 2.75, 95% CI 1.27-5.97, p = 0.01). Overall, the new PH definition using a threshold of mPAP >20 mmHg was associated with a higher risk of death (adj HR 2.71, 95% CI 1.26-5.80) than the previous definition (mPAP >25 mmHg, aHR: 1.35 95% CI 1.00-1.83, p = 0.05). CONCLUSIONS: One out of 8 patients with severe HF are reclassified as having PH following the 2018 WSPH. Patients with mPAP20-25 evaluated for heart transplantation displayed significant co-morbidities and high mortality rates.

Impact of the antiplatelet strategy following patent foramen ovale percutaneous closure.

AIMS: Temporary dual antiplatelet therapy (DAPT) is recommended following patent foramen ovale (PFO) percutaneous closure although its benefit, compared to single antiplatelet therapy (SAPT), has not been demonstrated in this setting. We aimed at assessing outcomes following PFO closure according to the antiplatelet strategy at discharge. METHODS AND RESULTS: The ambispective AIR-FORCE cohort included consecutive patients from seven centres in France and Canada undergoing PFO closure and discharged without anticoagulation. Patients treated in French and Canadian centres were mostly discharged with DAPT and SAPT, respectively. The primary endpoint was the composite of death, stroke, transient ischaemic attack, peripheral embolism, myocardial infarction, or BARC type ≥2 bleeding with up to 5 years of follow-up. The impact of the antiplatelet strategy on outcomes was evaluated with a marginal Cox model (cluster analyses per country) with inverse probability weighting according to propensity score. A total of 1532 patients (42.2% female, median age: 49 [40-57] years) were included from 2001 to 2022, of whom 599 (39.1%) were discharged with SAPT and 933 (60.9%) with DAPT, for ≤3 months in 894/923 (96.9%) cases. After a median follow-up of 2.4 [1.1-4.4] years, a total of 58 events were observed. In the weighted analysis, the rate of the primary endpoint up to 5 years was 7.8% in the SAPT strategy and 7.3% in the DAPT strategy (weighted hazard ratio 1.04, 95% confidence interval 0.59-1.83). CONCLUSION: The antiplatelet strategy following PFO closure did not seem to impact clinical outcomes, thus challenging the current recommendations of temporary DAPT.

Abatacept/Ruxolitinib and Screening for Concomitant Respiratory Muscle Failure to Mitigate Fatality of Immune-Checkpoint Inhibitor Myocarditis.

Immune-checkpoint-inhibitor (ICI)-associated myotoxicity involves the heart (myocarditis) and skeletal muscles (myositis), which frequently occur concurrently and are highly fatal. We report the results of a strategy that included identification of individuals with severe ICI myocarditis by also screening for and managing concomitant respiratory muscle involvement with mechanical ventilation, as well as treatment with the CTLA4 fusion protein abatacept and the JAK inhibitor ruxolitinib. Forty cases with definite ICI myocarditis were included with pathologic confirmation of concomitant myositis in the majority of patients. In the first 10 patients, using recommended guidelines, myotoxicity-related fatality occurred in 60%, consistent with historical controls. In the subsequent 30 cases, we instituted systematic screening for respiratory muscle involvement coupled with active ventilation and treatment using ruxolitinib and abatacept. The abatacept dose was adjusted using CD86 receptor occupancy on circulating monocytes. The myotoxicity-related fatality rate was 3.4% (1/30) in these 30 patients versus 60% in the first quartile (P < 0.0001). These clinical results are hypothesis-generating and need further evaluation. SIGNIFICANCE: Early management of respiratory muscle failure using mechanical ventilation and high-dose abatacept with CD86 receptor occupancy monitoring combined with ruxolitinib may be promising to mitigate high fatality rates in severe ICI myocarditis. See related commentary by Dougan, p. 1040. This article is highlighted in the In This Issue feature, p. 1027.

Predictors of Clinical Success After Transcatheter Paravalvular Leak Closure: An International Prospective Multicenter Registry.

BACKGROUND: Transcatheter closure of a symptomatic prosthetic paravalvular leak (PVL) is feasible, but there is presently no conclusive evidence to show consistent efficacy. We aimed to identify predictors of clinical success after transcatheter PVL closure. METHODS: Consecutive patients referred to 24 European centers for transcatheter PVL closure in 2017 to 2019 were included in a prospective registry (Fermeture de Fuite ParaProthétique, FFPP). Clinical success was absence of any of the following within 1 month: re-admission for heart failure, blood transfusion, open-heart valvular surgery, and death. RESULTS: We included 216 symptomatic patients, who underwent 238 percutaneous PVL closure procedures on the mitral (64.3%), aortic (34.0%), or tricuspid (1.7%) valve. Symptoms were heart failure, hemolytic anemia, or both in 48.9%, 7.8%, and 43.3% of patients, respectively. One, 2, and 3 leaks were treated during the same procedure in 69.6%, 26.6%, and 3.8% of patients, respectively. The PVL was pinpoint or involved 1/8 or 1/4 of the valve circumference in 18.6%, 52.4%, and 28.1% of cases, respectively. The most frequently used devices were the Vascular Plug 3, Ventricular Septal Defect Occluder, Vascular Plug 2, and Paravalvular Leak Device (45.0%, 16.6%, 14.2%, and 13.6% of cases, respectively). Successful device(s) implantation with leak reduction to ≤grade 2 was obtained in 85.0% of mitral and 91.4% of aortic procedures, respectively (P=0.164); with major periprocedural adverse event rates of 3.3% and 1.2%, respectively (P=0.371); and clinical success rates of 70.3% and 88.0%, respectively (P=0.004). By multivariate analysis, technical failure, mechanical valve, and hemolytic anemia were independently associated with absence of clinical success (odds ratios [95% CIs], 7.7 [2.0-25.0]; P=0.002; 3.6 [1.1-11.1]; P=0.036; and 3.7 [1.2-11.9]; P=0.025; respectively). CONCLUSIONS: Transcatheter PVL closure is efficient and safe in symptomatic patients but is associated with a lower clinical success rate in patients with hemolysis and/or a mechanical valve. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifiers: NCT05089136.

Supraventricular Arrhythmia Following Patent Foramen Ovale Percutaneous Closure.

BACKGROUND: Randomized studies have reported low rates of atrial fibrillation (AF) after patent foramen ovale (PFO) closure (<6%) but have relied on patient-reported symptomatic episodes, so the true incidence and timing of AF after PFO closure remain unknown. OBJECTIVES: The aim of this study was to prospectively determine the incidence, timing, and determinants of supraventricular arrhythmia following PFO closure on the basis of loop recorder monitoring. METHODS: Cardiac monitoring was proposed to all patients after PFO closure from June 2018 to October 2021 at a single center by means of implantable loop recorder monitoring in patients considered at higher risk for AF (age ≥ 55 years, associated cardiovascular risk factors, prior palpitations, or documented supraventricular ectopic activity) or 4-week external loop recorder monitoring in other patients. The primary endpoint was the incidence of AF, atrial flutter, or supraventricular tachycardia lasting >30 seconds within 28 days of the procedure. Determinants of the primary endpoint were assessed using a stepwise logistic regression model. RESULTS: A total of 225 patients were included. The primary endpoint occurred in 47 patients (20.9%), including 13 (9.9%) and 24 (28.9%) among patients monitored with external loop recorders and implantable loop recorders, respectively. Overall, the median delay from procedure to arrhythmia was 14.0 days (IQR: 6.5-19.0 days), and one-half of these patients reported symptomatic episodes. Determinants of the primary endpoint were older age (adjusted OR: 1.67 per 10-year increase; 95% CI: 1.18-2.36), device left disc diameter ≥25 mm (adjusted OR: 2.67; 95% CI: 1.19-5.98) and male sex (adjusted OR: 4.78; 95% CI: 1.96-11.66). CONCLUSIONS: Using loop recorder monitoring for ≥28 days, supraventricular arrhythmia was diagnosed in 1 in 5 patients, with a median delay of 14 days, suggesting that this postprocedural event has so far been underestimated.

Infective endocarditis in pregnant women without intravenous drug use: a multicentre retrospective case series.

OBJECTIVES: To describe the clinical features and outcomes of infective endocarditis (IE) in pregnant women who do not inject drugs. METHODS: A multinational retrospective study was performed at 14 hospitals. All definite IE episodes between January 2000 and April 2021 were included. The main outcomes were maternal mortality and pregnancy-related complications. RESULTS: Twenty-five episodes of IE were included. Median age at IE diagnosis was 33.2 years (IQR 28.3-36.6) and median gestational age was 30 weeks (IQR 16-32). Thirteen (52%) patients had no previously known heart disease. Sixteen (64%) were native IE, 7 (28%) prosthetic and 2 (8%) cardiac implantable electronic device IE. The most common aetiologies were streptococci (n = 10, 40%), staphylococci (n = 5, 20%), HACEK group (n = 3, 12%) and Enterococcus faecalis (n = 3, 12%). Twenty (80%) patients presented at least one IE complication; the most common were heart failure (n = 13, 52%) and symptomatic embolism other than stroke (n = 4, 16%). Twenty-one (84%) patients had surgery indication and surgery was performed when indicated in 19 (90%). There was one maternal death and 16 (64%) patients presented pregnancy-related complications (11 patients ≥1 complication): 3 pregnancy losses, 9 urgent Caesarean sections, 2 emergency Caesarean sections, 1 fetal death, and 11 preterm births. Two patients presented a relapse during a median follow-up of 3.1 years (IQR 0.6-7.4). CONCLUSIONS: Strict medical surveillance of pregnant women with IE is required and must involve a multidisciplinary team including obstetricians and neonatologists. Furthermore, the potential risk of IE during pregnancy should never be underestimated in women with previously known underlying heart disease.

Outcomes Following Patent Foramen Ovale Percutaneous Closure According to the Delay From Last Ischemic Event.

BACKGROUND: Randomised controlled trials evaluating percutaneous closure of patent foramen ovale (PFO) have included only patients with a recent embolic event. We aimed to evaluate outcomes after percutaneous PFO closure according to the delay from the last embolic episode. METHODS: This international ambispective cohort included consecutive patients from 2 centres in France and Canada undergoing PFO closure for secondary prevention of a paradoxical embolic event. The primary end point was the composite of stroke or transient ischemic attack (TIA). A logistic regression model was used to evaluate determinants of late PFO closure procedures. RESULTS: A total of 1179 patients (mean age 49 ± 12.7 years; 44.4% female) underwent PFO closure from 2001 to 2021. The median delay from last embolic event to procedure was 6.0 (interquartile range 3.4-11.2) months. The determinants of late PFO closure procedure were the centre (France vs Canada; adjusted odds ratio [aOR] 1.65, 95% confidence interval [CI] 1.25-2.19), year of procedure (since 2018 vs before 2018; aOR 1.43, 95% CI 1.08-1.90), female sex (aOR 1.63, 95% CI 1.28-2.07), and lower risk of paradoxical embolism score (aOR 1.10, 95% CI 1.03-1.19). After a median follow-up of 2.61 (1.13-7.25) years, the incidence rate of first stroke or TIA did not differ between early and late PFO procedures, with 0.51 vs 0.29 events per 100 patient-years, respectively (incidence rate ratio 1.74, 95% CI 0.66-5.08; P = 0.24), and the timing of PFO closure was not associated with the occurrence of stroke or TIA in univariate analysis (hazard ratio 0.54, 95% CI 0.22-1.34) for late vs early closure). CONCLUSIONS: This analysis provides indirect evidence that the delay from the last ischemic event does not affect outcomes after PFO closure for secondary prevention.

Altered cardiac reserve is a determinant of exercise intolerance in sickle cell anaemia patients.

BACKGROUND: The underlying mechanisms of exercise intolerance in sickle cell anaemia (SCA) patients are complex and not yet completely understood. While latent heart failure at rest could be unmasked upon exercise, most previous studies assessed cardiac function at rest. We aimed to investigate exercise cardiovascular reserve as a potential contributor to exercise intolerance in adult SCA patients. METHODS: In this observational prospective study, we compared prospectively 60 SCA patients (median age 31 years, 60% women) to 20 matched controls. All subjects underwent symptom-limited combined exercise echocardiography and oxygen uptake (VO2 ) measurements. Differences between arterial and venous oxygen content (C(a-v)O2 ) were calculated. Cardiac reserve was defined as the absolute change in cardiac index (Ci) from baseline to peak exercise. RESULTS: Compared to controls, SCA patients demonstrated severe exercise intolerance (median peakVO2 , 34.3 vs. 19.7 ml/min/kg, respectively, p < .0001). SCA patients displayed heterogeneously increased Ci from rest to peak exercise (median +5.8, range 2.6 to 10.6 L/min/m²) which correlated with peakVO2 (r = 0.71, p < .0001). In contrast, the C(a-v)O2 exercise reserve was homogenously reduced and did not correlate with peakVO2 (r = 0.18, p = .16). While haemoglobin level and C(a-v)O2 were similar in SCA subgroups, SCA patients in the lower VO2 tertile had chronotropic incompetence and left ventricular diastolic dysfunction (left atrial peak longitudinal strain was reduced, and both E/e' ratio and left atrial volume index were increased) and were characterized by a reduced cardiac reserve, +5.0[4.2-5.5] compared to +6.7[5.5-7.8] L/min/m² for the rest of the patient cohort, p < .0001. CONCLUSIONS: Altered cardiac reserve due to chronotropic incompetence and left ventricular diastolic dysfunction seems to be an important determinant of exercise intolerance in adult SCA patients.

Hemodynamic and biological correlates of glomerular hyperfiltration in sickle cell patients before and under renin-angiotensin system blocker.

Glomerular hyperfiltration alone or associated with albuminuria is a well-known feature of sickle cell associated nephropathy. Though, glomerular hyperfiltration is currently considered to be related to a high renal plasma flow and chronic hemolysis, cardiac output influence on measured glomerular filtration rate (mGFR) have not been investigated so far. Thirty seven homozygous sickle cell patients (SCA) from the RAND study investigated before and under angiotensin converting enzyme inhibitor (ACEI) were included. Both mGFR and cardiac index (CI) were high (> 110 ml/min/1.73 m2 and > 3.5 l/m2 in 81% and 97% of cases) with low systemic vascular resistance (SVR) (< 700 dynes/s/cm-5) in 38% of cases. mGFR association with CI and SVR were significant at baseline (respectively ρ: 0.44, p = 0.008 and ρ: - 0.37, p = 0.02) and under ACEI (p = 0.007 and 0.01 respectively), in accordance with previous data showing that hyperfiltration was linked to an increased glomerular perfusion and a glomerulomegaly rather than increased capillary hydrostatic pressure. Of notice, after adjustment on CI, mGFR remained associated with reticulocyte count and albuminuria under ACEI (p = 0.006 and 0.02 respectively). Our results suggest that hyperfiltration is tightly linked to an increased cardiac output which may account for an increased renal blood flow. Chronic hemolysis could be a relevant factor accounting for hyperfiltration potentially acting on glomerular enlargement which appears as a key factor. Our data suggest that cardiac output assessment is a relevant tool in the routine management and monitoring of SCA nephropathy.

Risk factors for CKD stage II onset in a prospective cohort of homozygous sickle cell adults.

Prevalence of renal impairment is increasing with aging in sickle cell anemia (SCA) patients, and is responsible for a high morbidity and mortality. However, sickle cell nephropathy's natural course remains mostly unknown. We conducted a prospective observational cohort study aimed to identify risk factors for CKD stage II in a cohort of SCA patients. Baseline clinical and biological parameters were collected. Renal parameters were updated at each visit. Risk factors were analyzed using the Cox model. Five-hundred and thirty-five SCA patients were included with a median follow-up of 5.33 (IQR:2.10-8.13) years. Median age was 22 (IQR:19-30) years old. Glomerular hyperfiltration was detected in 299 (55.9%) patients, microalbuminuria and macroalbuminuria in 180 (34%) and 67 (12.7%) patients respectively. During follow up, CKD stage II onset was detected in 39 patients (7.3%). Risk factors for CKD stage II after adjustment on baseline eGFR and age were macroalbuminuria HR: 3.89 [95% CI: 1.61;9.43], diastolic blood pressure (DBP) above 70 mm Hg HR: 2.02 [1.02-3.971], LDH (for 100 IU/L increase) HR: 1.28 [1.12;1.48] and tricuspid regurgitation velocity >2.5 m/sec HR: 2.89 [1.20-6.99]. Multivariate analysis also found age as a strong independent risk factor with HR: (per year increase) 1.13 [1.09;1.16] and a 13.3-fold increase above 30 years (p < 0.001). Our results show a high incidence of CKD stage II with aging, with a strong significant risk increase after 30-years-old, and pinpoint baseline DBP, macroalbuminuria and increased LDH as independent risk factors raising the issue of optimal blood pressure targets for SCA patients.

HIV Infection and Long-Term Residual Cardiovascular Risk After Acute Coronary Syndrome.

Background It is unclear whether HIV infection affects the long-term prognosis after an acute coronary syndrome (ACS). The objective of the current study was to compare rates of major adverse cardiac and cerebrovascular events after a first ACS between people living with HIV (PLHIV) and HIV-uninfected (HIV-) patients, and to identify determinants of cardiovascular prognosis. Methods and Results Consecutive PLHIV and matched HIV- patients with a first episode of ACS were enrolled in 23 coronary intensive care units in France. Patients were matched for age, sex, and ACS type. The primary end point was major adverse cardiac and cerebrovascular events (cardiac death, recurrent ACS, recurrent coronary revascularization, and stroke) at 36-month follow-up. A total of 103 PLHIV and 195 HIV- patients (mean age, 49 years [SD, 9 years]; 94.0% men) were included. After a mean of 36.6 months (SD, 6.1 months) of follow-up, the risk of major adverse cardiac and cerebrovascular events was not statistically significant between PLHIV and HIV- patients (17.8% and 15.1%, P=0.22; multivariable hazard ratio [HR], 1.60; 95% CI, 0.67-3.82 [P=0.29]). Recurrence of ACS was more frequent among PLHIV (multivariable HR, 6.31; 95% CI, 1.32-30.21 [P=0.02]). Stratified multivariable Cox models showed that HIV infection was the only independent predictor for ACS recurrence. PLHIV were less likely to stop smoking (47% versus 75%; P=0.01) and had smaller total cholesterol decreases (-22.3 versus -35.0 mg/dL; P=0.04). Conclusions Although the overall risk of major adverse cardiac and cerebrovascular events was not statistically significant between PLHIV and HIV- individuals, PLHIV had a higher rate of recurrent ACS. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT00139958.

Reduced Rivaroxaban Dose Versus Dual Antiplatelet Therapy After Left Atrial Appendage Closure: ADRIFT a Randomized Pilot Study.

BACKGROUND: Percutaneous left atrial appendage closure (LAAC) exposes to the risk of device thrombosis in patients with atrial fibrillation who frequently have a contraindication to full anticoagulation. Thereby, dual antiplatelet therapy (DAPT) is usually preferred. No randomized study has evaluated nonvitamin K antagonist oral anticoagulant after LAAC, and we decided to evaluate the efficacy and safety of reduced doses of rivaroxaban after LAAC. METHODS: ADRIFT (Assessment of Dual Antiplatelet Therapy Versus Rivaroxaban in Atrial Fibrillation Patients Treated With Left Atrial Appendage Closure) is a multicenter, phase IIb study, which randomized 105 patients after successful LAAC to either rivaroxaban 10 mg (R10, n=37), rivaroxaban 15 mg (R15, n=35), or DAPT with aspirin 75 mg and clopidogrel 75 mg (n=33). The primary end point was thrombin generation (prothrombin fragments 1+2) measured 2 to 4 hours after drug intake, 10 days after treatment initiation. Thrombin-antithrombin complex, D-dimers, rivaroxaban concentrations were also measured at 10 days and 3 months. Clinical end points were evaluated at 3-month follow-up. RESULTS: The primary end point was reduced with R10 (179 pmol/L [interquartile range (IQR), 129-273], P<0.0001) and R15 (163 pmol/L [IQR, 112-231], P<0.0001) as compared with DAPT (322 pmol/L [IQR, 218-528]). We observed no significant reduction of the primary end point between R10 and R15 while rivaroxaban concentrations increased significantly from 184 ng/mL (IQR, 127-290) with R10 to 274 ng/mL (IQR, 192-377) with R15, P<0.0001. Thrombin-antithrombin complex and D-dimers were numerically lower with both rivaroxaban doses than with DAPT. These findings were all confirmed at 3 months. The clinical end points were not different between groups. A device thrombosis was noted in 2 patients assigned to DAPT. CONCLUSIONS: Thrombin generation measured after LAAC was lower in patients treated by reduced rivaroxaban doses than DAPT, supporting an alternative to the antithrombotic regimens currently used after LAAC and deserves further evaluation in larger studies. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03273322.

Antithrombotic Therapy for Patients With Left Ventricular Mural Thrombus.

BACKGROUND: Contemporary data are lacking regarding the prognosis and management of left ventricular thrombus (LVT). OBJECTIVES: The purpose of this study was to quantify the effect of anticoagulation therapy on LVT evolution using sequential imaging and to determine the impact of LVT regression on the incidence of thromboembolism, bleeding, and mortality. METHODS: From January 2011 to January 2018, a comprehensive computerized search of LVT was conducted using 90,065 consecutive echocardiogram reports. Only patients with a confirmed LVT were included after imaging review by 2 independent experts. Major adverse cardiovascular events (MACE), which included death, stroke, myocardial infarction, or acute peripheral artery emboli, were determined as well as major bleeding events (BARC ≥3) and all-cause mortality rates. RESULTS: There were 159 patients with a confirmed LVT. Patients were treated with vitamin K antagonists (48.4%), parenteral heparins (27.7%), and direct oral anticoagulants (22.6%). Antiplatelet therapy was used in 67.9% of the population. A reduction of the LVT area from baseline was observed in 121 patients (76.1%), and total LVT regression occurred in 99 patients (62.3%) within a median time of 103 days (interquartile range: 32 to 392 days). The independent correlates of LVT regression were a nonischemic cardiomyopathy (hazard ratio [HR]: 2.74; 95% confidence interval [CI]: 1.43 to 5.26; p = 0.002) and a smaller baseline thrombus area (HR: 0.66; 95% CI: 0.45 to 0.96; p = 0.031). The frequency of MACE was 37.1%; mortality 18.9%; stroke 13.3%; and major bleeding 13.2% during a median follow-up of 632 days (interquartile range: 187 to 1,126 days). MACE occurred in 35.4% and 40.0% of patients with total LVT regression and those with persistent LVT (p = 0.203). A reduced risk of mortality was observed among patients with total LVT regression (HR: 0.48; 95% CI: 0.23 to 0.98; p = 0.039), whereas an increased major bleeding risk was observed among patients with persistent LVT (9.1% vs. 12%; HR 0.34; 95% CI: 0.14 to 0.82; p = 0.011). A left ventricular ejection fraction ≥35% (HR: 0.46; 95% CI: 0.23 to 0.93; p = 0.029) and anticoagulation therapy >3 months (HR: 0.42; 95% CI: 0.20 to 0.88; p = 0.021) were independently associated with less MACE. CONCLUSIONS: The presence of LVT was associated with a very high risk of MACE and mortality. Total LVT regression, obtained with different anticoagulant regimens, was associated with reduced mortality.