Intravenous adenosine: Continuous infusion and low dose bolus administration for determination of coronary vasodilator reserve in patients with and without coronary artery disease

AbstractTo assess the use of adenosine as an alternative agent for determination of coronary vasodilator reserve, hemodynamics and coronary blood flow velocity were measured at rest and during peak hyperemic responses to continuous intravenous adenosine infusion (50, 100 and 150 μg/kg per min for 3 min) and intracoronary papaverine (10 mg) in 34 patients (17 without [group 1]and 17 with [group 2]significant left coronary artery disease), and in 17 patients (11 without and 6 with left coronary artery disease) after low dose (2.5 mg) intravenous bolus injection of adenosine.The maximal adenosine dose did not change mean arterial pressure (−10 ± 14% and −6 ± 12% for groups 1 and 2, respectively) but increased the heart rate (15 ± 18% and 13 ±16%, respectively). For continuous adenosine infusions, mean coronary flow velocity increased 64 ± 104%, 122 ± 94% and 198 ± 59% and 15 ± 51%, 110 ± 95% and 109 ± 86% in groups 1 and 2, respectively for each of the three doses. Mean coronary flow velocity increased significantly after 100 and 150 μg/kg of adenosine and 10 mg of intracoronary papaverine (48 ± 25, 52 ±19 and 54 ± 21 cm/s, respectively; all p < 0.05 vs. baseline) and was significantly higher than in group 2 (37 ± 24, 32 ± 16, 41 ± 23 cm/s; all p < 0.05 vs. group 1). The coronary vasodilator reserve ratio (calculated as the ratio of hyperemic to basal mean flow velocity) for adenosine and papaverine was 2.94 ± 1.50 and 2.94 ± 1.00, respectively, in group 1 and was significantly and similarly reduced in group 2 (2.16 ± 0.81 and 2.38 ± 0.78, respectively; both p < 0.05 vs. group 1). Low dose bolus injection of adenosine increased mean velocity equivalenty to that after continuous infusion of 100 μg/kg, but less than after papaverine. There was a strong correlation between adenosine infusion and papaverine for both mean coronary flow velocity and coronary vasodilator reserve ratio (r2= 0.871 and 0.325; SEE = 0.068 and 0.189, respectively; both p < 0.0005).No patient had significant arrhythmias or prolongation of the corrected QT (QTc) interval with adenosine, but papaverine increased the QTc interval from 445 ± 44 to 501 ± 43 ms (p < 0.001 vs. both maximal adenosine and baseline) and produced nonsustained ventricular tachycardia in one patient.These data indicate that intravenous adenosine in doses >100 μg/kg (and in low dose bolus injections) for most patients is nearly equivalent to intracoronary papaverine without producing QTc prolongation, making this agent a potentially superior and safer alternative to intracoronary papaverine for determination of coronary vasodilator reserve

Enhanced coronary blood flow velocity during intraaortic balloon counterpulsation in critically III patients

AbstractObjectives. The aim of this study was to assess coronary blood flow during intraaortic balloon counterpulsation by direct measurement.Background. In a majority of human studies, increased coronary blood flow during intraaortic balloon counterpulsation measured by indirect techniques has not been consistently demonstrated.Methods. Hemodynamic variables and coronary blood flow velocity (20-MHz Doppler-tipped catheter) data were measured in 19 patients requiring intraaortic balloon pumping for clinical indications (11 patients had acute myocardial infarction [9 with shock], 6 had unstable angina, 1 had acute mitral regurgitation and 1 was at high risk undergoing angioplasty). Hemodynamic data, mean and phasic diastolic flow velocity and velocity-time integrals (computed from digitized waveforms) were analyzed during periods of 1:1 balloon counterpulsation.Results. Intraaortic balloon pumping decreased systolic pressure (6 ± 10%, p < 0.001) and increased diastolic pressure (80 ± 30% from baseline, p < 0.001) without changing RR interval. Peak phasic, mean coronary flow velocity and diastolic flow velocity integral were significantly increased (115 ± 115%, 67 ± 61%, 103 ± 81%, respectively, all p < 0.001) during intraaortic balloon pumping. In addition, although a wide splay of data was evident due to operator set variations in ballon inflation and deflation timing, the greater increases in diastolic flow velocity integral (DFV1) occurred in patients with basal systolic pressure ≤90 mm Hg (%ADFV1= 102 - O.1[unaugmented systolic pressure], SEE = 21.7 mm Hg, r = 0.30, p < 0.001).Conclusions. Intraaortic balloon pumping unequivocally and significantly augments proximal coronary blood flow velocity, nearly doubling the coronary flow velocity integral in most patients. This mechanism may be a significant means of ischemia relief in hypotensive patients

Early ambulation after 5 French diagnostic cardiac catheterization: Results of a multicenter trial

AbstractBecause earlier ambulation and discharge after cardiac catheterization may result in the increased utilization of outpatient facilities, a prospective five center clinical pilot trial assessing the safety and outcome of early ambulation after routine left heart catheterization was performed in 287 patients. Catheterization routines at each clinical center were unchanged throughout the study. After the diagnostic catheterization using 5 French (F), preformed, large lumen catheters and arterial puncture compression (mean 15 min, range 5 to 52), 260 patients were ambulated by a physician at a mean time of 2.6 h (range 1.8 to 3.1) after catheterization. Follow-up examination or a phone call 24 to 72 h later was performed to assess late results.The mean age of the patients was 58 years (range 25 to 91);166 (58%) were men. Left ventricular ejection fraction was 54 ± 15%. One hundred twenty-seven patients (44%) received intravenous heparin (1,500 to 5,000 U as an intravenous bolus) and 136 (47%) received aspirin.Major complications included transient ischemic attack (one patient) and ventricular tachycardia requiring cardio-version during ventriculography (two patients). A small hematoma (<5.0 cm) after ambulation occurred early (from compression to standing) in 14 patients (5%; 9 received heparin, 8 were taking aspirin) and later (after standing to 72 h) in 9 patients (3, 2 receiving heparin, 2 taking aspirin). Five patients with a hematoma had studies with a 6F sheath. No patient required surgical intervention for early or late hematoma. Only three patients (1%) needed a 7F or 8F catheter because of suboptimal 5F coronary angiography. Ninety-two percent of patients had a complete study with the 5F catheters.These results indicate that early ambulation after large lumen 5F femoral left heart catheterization was safe, with minimal postprocedural complications and without compromising angiographic data quality. Early ambulation has the potential to improve outpatient catheterization cost factors by early discharge and increased facility utilization

Arrhythmia monitoring and outcome after myocardial infarction (BIO|GUARD-MI): a randomized trial

OBJECTIVES: Cardiac arrhythmias predict poor outcome after myocardial infarction (MI). We studied if arrhythmia monitoring with an insertable cardiac monitor (ICM) can improve treatment and outcome.DESIGN: BIO|GUARD-MI was a randomized, international open-label study with blinded outcome assessment.SETTING: Tertiary care facilities monitored the arrhythmias, while the follow-up remained with primary care physicians.PARTICIPANTS: Patients after ST-elevation (STEMI) or non-ST-elevation MI with an ejection fraction &gt;35% and a CHA2DS2-VASc score ≥4 (men) or ≥5 (women).INTERVENTIONS: Patients were randomly assigned to receive or not receive an ICM in addition to standard post-MI treatment. Device-detected arrhythmias triggered immediate guideline recommended therapy changes via remote monitoring.MAIN OUTCOME MEASURES: MACE, defined as a composite of cardiovascular death or acute unscheduled hospitalization for cardiovascular causes.RESULTS: 790 patients (mean age 71 years, 72% male, 51% non-STEMI) of planned 1,400 pts were enrolled and followed for a median of 31.6 months. At 2 years, 39.4% of the device group and 6.7% of the control group had their therapy adapted for an arrhythmia [hazard ratio (HR) = 5.9, P &lt; 0.0001]. Most frequent arrhythmias were atrial fibrillation, pauses and bradycardia. The use of an ICM did not improve outcome in the entire cohort (HR = 0.84, 95%-CI: 0.65-1.10; P = 0.21). In secondary analysis, a statistically significant interaction of the type of infarction suggests a benefit in the pre-specified non-STEMI subgroup. Risk factor analysis indicates that this may be connected to the higher incidence of MACE in patients with non-STEMI.CONCLUSIONS: The burden of asymptomatic but actionable arrhythmias is large in post-infarction patients. However, arrhythmia monitoring with an ICM did not improve outcome in the entire cohort. Post-hoc analysis suggests that it may be beneficial in non-STEMI patients or other high-risk subgroups.CLINICAL TRIAL REGISTRATION: [https://www.clinicaltrials.gov/ct2/show/NCT02341534], NCT02341534.</p

Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial

Background: Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure. Methods: The SELECT trial was a randomised, double-blind, multicentre, placebo-controlled, event-driven phase 3 trial in 41 countries. Adults aged 45 years and older, with a BMI of 27 kg/m2 or greater and established cardiovascular disease were eligible for the study. Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo. In a prespecified analysis, we examined the effect of semaglutide compared with placebo in patients with and without a history of heart failure at enrolment, subclassified as heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, or unclassified heart failure. Endpoints comprised MACE (a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death); a composite heart failure outcome (cardiovascular death or hospitalisation or urgent hospital visit for heart failure); cardiovascular death; and all-cause death. The study is registered with ClinicalTrials.gov, NCT03574597. Findings: Between Oct 31, 2018, and March 31, 2021, 17 604 patients with a mean age of 61·6 years (SD 8·9) and a mean BMI of 33·4 kg/m2 (5·0) were randomly assigned to receive semaglutide (8803 [50·0%] patients) or placebo (8801 [50·0%] patients). 4286 (24·3%) of 17 604 patients had a history of investigator-defined heart failure at enrolment: 2273 (53·0%) of 4286 patients had heart failure with preserved ejection fraction, 1347 (31·4%) had heart failure with reduced ejection fraction, and 666 (15·5%) had unclassified heart failure. Baseline characteristics were similar between patients with and without heart failure. Patients with heart failure had a higher incidence of clinical events. Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (hazard ratio [HR] 0·72, 95% CI 0·60-0·87 for MACE; 0·79, 0·64-0·98 for the heart failure composite endpoint; 0·76, 0·59-0·97 for cardiovascular death; and 0·81, 0·66-1·00 for all-cause death; all pinteraction&gt;0·19). Treatment with semaglutide resulted in improved outcomes in both the heart failure with reduced ejection fraction (HR 0·65, 95% CI 0·49-0·87 for MACE; 0·79, 0·58-1·08 for the composite heart failure endpoint) and heart failure with preserved ejection fraction groups (0·69, 0·51-0·91 for MACE; 0·75, 0·52-1·07 for the composite heart failure endpoint), although patients with heart failure with reduced ejection fraction had higher absolute event rates than those with heart failure with preserved ejection fraction. For MACE and the heart failure composite, there were no significant differences in benefits across baseline age, sex, BMI, New York Heart Association status, and diuretic use. Serious adverse events were less frequent with semaglutide versus placebo, regardless of heart failure subtype. Interpretation: In patients with atherosclerotic cardiovascular diease and overweight or obesity, treatment with semaglutide 2·4 mg reduced MACE and composite heart failure endpoints compared with placebo in those with and without clinical heart failure, regardless of heart failure subtype. Our findings could facilitate prescribing and result in improved clinical outcomes for this patient group. Funding: Novo Nordisk

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

A retrospective review of patients with massive and submassive pulmonary embolism treated with AngioJet rheolytic thrombectomy with decreased complications due to changes in thrombolytic use and procedural modifications

ObjectivesA retrospective review of treatment of patients with massive or submassive pulmonary embolism (PE) using AngioJet rheolytic thrombectomy (ART) system with procedural modifications to improve on the previously reported outcomes.Materials and MethodsThirteen patients underwent emergent pulmonary artery thrombectomy for massive and submassive PE using ART with pharmacological and procedural modification, in comparison to prior reports. The modifications included the selective use of the Solent Omni AngioJet device in all subjects, distal contrast angiography via the AngioJet catheter before device activation, and limited short run times. Thrombolytic therapy was not used in any patient. Patients were monitored for short- and long-term outcomes. Long-term clinical follow-up and evaluation for persistent pulmonary hypertension with echocardiography was performed.ResultsThe pharmacological and procedural modifications resulted in a favorable clinical response without any major complications and without any mortality. Procedure-related anemia (mean hemoglobin drop of 0.49 g/dl) was the only significant minor complication noted. There were no bleeding complications and no transfusion requirement. On a six-month follow-up, there was no mortality, and there were significant reductions in the pulmonary artery pressures.ConclusionMajor and minor complications were reduced compared to prior reports using ART. A modified ART approach towards treatment of high-risk PE appears promising both in terms of efficacy and safety.</jats:sec