Clinical implementation of partial oral treatment in infective endocarditis: the Danish POETry study.

BACKGROUND AND AIMS: In the Partial Oral Treatment of Endocarditis (POET) trial, stabilized patients with left-sided infective endocarditis (IE) were randomized to oral step-down antibiotic therapy (PO) or conventional continued intravenous antibiotic treatment (IV), showing non-inferiority after 6 months. In this study, the first guideline-driven clinical implementation of the oral step-down POET regimen was examined. METHODS: Patients with IE, caused by Staphylococcus aureus, Enterococcus faecalis, Streptococcus spp. or coagulase-negative staphylococci diagnosed between May 2019 and December 2020 were possible candidates for initiation of oral step-down antibiotic therapy, at the discretion of the treating physician. The composite primary outcome in patients finalizing antibiotic treatment consisted of embolic events, unplanned cardiac surgery, relapse of bacteraemia and all-cause mortality within 6 months. RESULTS: A total of 562 patients [median age 74 years (IQR, interquartile range, 65-80), 70% males] with IE were possible candidates; PO was given to 240 (43%) patients and IV to 322 (57%) patients. More patients in the IV group had IE caused by S. aureus, or had an intra-cardiac abscess, or a pacemaker and more were surgically treated. The primary outcome occurred in 30 (13%) patients in the PO group and in 59 (18%) patients in the IV group (P = .051); in the PO group, 20 (8%) patients died vs. 46 (14%) patients in the IV group (P = .024). PO-treated patients had a shorter median length of stay [PO 24 days (IQR 17-36) vs. IV 43 days (IQR 32-51), P < .001]. CONCLUSIONS: After clinical implementation of the POET regimen almost half of the possible candidates with IE received oral step-down antibiotic therapy. Patients in the IV group had more serious risk factors for negative outcomes. At 6-month follow-up, there was a numerically but not statistically significant difference towards a lower incidence of the primary outcome, a lower incidence of all-cause mortality and a reduced length of stay in the PO group. Due to the observational design of the study, the lower mortality may to some extent reflect selection bias and unmeasured confounding. Clinical implementation of PO regimens seemed feasible and safe.

Cardiac magnetic resonance imaging with standard imaging planes for mitral valve scallop pathology: interrater agreement and comparison with echocardiography.

Magnetic resonance imaging (CMR) is applied in mitral valve regurgitation (MR) to quantify regurgitation volume/fraction and cardiac volumes, but individual scallop pathology is evaluated by echocardiography. To evaluate CMR for determination of individual scallop pathology, interrater variability on evaluation of scallop pathology from echocardiography and a standard clinical CMR protocol including a transversal stack was compared. 318 mitral scallops from 53 patients with primary MR were evaluated by two cardiologists evaluating echocardiography scans and two other cardiologists evaluating CMR scans (blinded). Inter-rater variability was determined with percentage agreement and Cohen's kappa. In evaluable scallops, interrater agreement on the diagnosis of a prolapsing and/or flail scallop was 77-87% and kappa values of 0.27-0.67, irrespective of physician or modality. Important differences between modalities were primarily related to CMR-evaluators judging the A3 and the P3 to be normal when echocardiography demonstrated prolapsing or even flail scallops; poor imaging of calcification; and flailed scallops occasionally being undetected with CMR since the flow-voids may mask the scallop. Inter-rater agreement for scallop pathology in primary MR is comparable for echocardiography and standard magnetic resonance imaging scans, but CMR has important pitfalls relating to evaluation of A3 and P3 scallops, and suffers from poor visualization of calcification and lower spatial resolution than echo. CMR with standard planes cannot replace CMR with longitudinal planes or echo for the evaluation of specific scallop pathology in severe primary MR.

Quantification of mitral valve regurgitation by 2D and 3D echocardiography compared with cardiac magnetic resonance a systematic review and meta-analysis.

By means of systematic literature review and meta-analysis, we compared results of studies examining different echocardiographic methods assessing severity of mitral valve regurgitation volume (MVR) with cardiac magnetic resonance imaging (CMR) as standard reference. A systematic search of electronic databases revealed twenty studies eligible for meta-analysis. Results of 2D- and 3D-trans-thoracic (TTE) and trans-esophageal echocardiographic (TEE) proximal isovelocity surface area (PISA) and volumetric methods were compared with CMR. Mean differences (ml) with 95% limits of agreement (LoA) derived from Bland-Altman tests and correlations coefficients [(R) 95% confidence interval (CI)] were pooled together. Overall 1187 patients [mean age = 59 ± 13 years and 678(57%) males] with primary or secondary mild to severe MVR were included. Comparing all echocardiographic methods with CMR showed an overestimation and moderate agreement with difference and 95% LoA of 8.05(- 3.40, 19.49) ml, R = 0.73(95% CI 0.71-0.76) p < 0.001. 3D-PISA followed by 3D-volumetric methods showed the better agreement with an underestimation of - 3.20(- 12.33, 5.92) ml, R = 0.84(95% CI 0.78-0.89) p < 0.001 and overestimation of 3.73(- 9.17, 16.61) ml, R = 0.90(95% CI 0.87, 0.94) p < 0.001, respectively. 2D-volumetric method showed the poorest agreement with difference and 95% LoA of 23.56(- 4.19, 51.31) ml, R = 0.64(95% CI 0.54-0.73) p < 0.001. In patients (n = 280) with severe MVR, 2D technique incorrectly estimated regurgitation volume severity in 106 (38%) compared to 4(14%) patients using 3D technique. Among echocardiographic methods 3D-PISA agreed best with CMR as reference, making 3D-PISA the most reliable method to quantify MVR. CMR can be considered in severe MVR where uncertainties arise and a decision-making prior valve surgery is required. Further powerful studies are needed to assess the accuracy of different echocardiographic methods.

The prognostic significance of lung function in stable heart failure outpatients.

BACKGROUND: This study investigated the impact on all-cause mortality of airflow limitation indicative of chronic obstructive pulmonary disease or restrictive spirometry pattern (RSP) in a stable systolic heart failure population. HYPOTHESIS: Decreased lung function indicates poor survival in heart failure. METHODS: Inclusion criteria: NYHA class II-IV and left ventricular ejection fraction (LVEF) < 45%. Prognosis was assessed with multivariate Cox proportional hazards models. Two criteria of obstructive airflow limitation were applied: FEV1 /FVC < 0.7 (GOLD), and FEV1 /FVC < lower limit of normality (LLN). RSP was defined as FEV1 /FVC > 0.7 and FVC<80% or FEV1 /FVC > LLN and FVC

Prevalence of airflow obstruction in patients with stable systolic heart failure.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an important differential diagnosis in heart failure (HF). However, routine use of spirometry in outpatient HF clinics is not implemented. The aim of the present study was to determine the prevalence of both airflow obstruction and non obstructive lung function impairment in patients with HF and to examine the effect of optimal medical treatment for HF on lung function parameters. METHODS: Consecutive patients with HF (ejection fraction (EF) < 45%) and New York Heart Association (NYHA) functional class II-IV at 10 different outpatient heart failure clinics were examined with spirometry at their first visit and after optimal medical treatment for HF was achieved. airflow obstruction was classified and graded according to the GOLD 2011 revision. RESULTS: Baseline spirometry was performed in 593 included patients and 71 (12%) had a clinical diagnosis of COPD. Mean age was 69 ± 11 years and mean EF was 30 ± 9%. Thirty-two % of the patients were active smokers and 53% were previous smokers. Mean FEV1 and FVC was 77.9 ± 1.7% and 85.4 ± 1.5% of predicted respectively. Obstructive pattern was observed in 233 (39%) of the patients. Of these, 53 patients (9%) had mild disease (GOLD I) and 180 (30%) patients had moderate to very severe disease (GOLD II-IV). No difference in spirometric variables was observed following up titration of medication. CONCLUSION: In stable patients with HF airflow obstruction is frequent and severely underdiagnosed. Spirometry should be considered in all patients with HF in order to improve diagnosis and treatment for concomitant pulmonary disease.

Iron Deficiency in COPD Associates with Increased Pulmonary Artery Pressure Estimated by Echocardiography.

OBJECTIVES: Iron deficiency (ID) might augment chronic pulmonary hypertension in chronic obstructive pulmonary disease (COPD). This observational study investigates the association between ID and systolic pulmonary artery pressure estimated by echocardiography in non-anaemic COPD outpatients. METHODS: Non-anaemic COPD patients (GOLD II-IV) with no history of cardiovascular disease were recruited from outpatient clinics. Iron deficiency was defined as ferritin<100µg/L. Pulmonary artery pressure was estimated from the tricuspid regurgitation maximum velocity (TR Vmax). Tricuspid regurgitation Vmax indicative of pulmonary hypertension was considered present for values ≥ 2.9 m/s. RESULTS: In a total of 75 included patients, 31 (41%) had ID. These patients had a significantly higher TR Vmax (3.02 vs. 2.77 m/s, p=0.01) and lower diffusion capacity of carbon monoxide (40% vs. 50% of predicted, p<0.01), though similar in age, sex, pack years, FEV1 and high-sensitive CRP (p>0.05). Ferritin inversely correlated with TR Vmax in ID patients (-0.37 (p=0.04)). The prevalence of TR Vmax ≥ 2.9 m/s was twice as high in patients with ID (58% vs. 29%) and odds ratio of pulmonary hypertension in ID (compared to no ID) was 3.3 (95% CI 1.3-8.6, p=0.015). CONCLUSION: Iron deficiency in non-anaemic COPD patients was associated with a modest increase in systolic pulmonary artery pressure and limitation of diffusion capacity.

5-Fluorouracil-induced acute reversible heart failure not explained by coronary spasms, myocarditis or takotsubo: lessons from MRI.

A 69-year-old woman presented with arterial hypotension, pulmonary oedema and a severely depressed left ventricular ejection fraction (LVEF) of 25% only 3 days after having received her first treatment for colorectal cancer with 5-fluorouracil (5-FU)-based therapy. The ECG demonstrated widespread ST-segment depression and echocardiography showed uniform hypokinesia of all left ventricular (LV) myocardial segments without signs of regional LV ballooning. Coronary angiography was normal and the patient gained full recovery after receiving treatment with heart failure medication. Interestingly, cardiac MRI scan 9 days later showed a normal LVEF with signs of neither myocardial oedema nor necrosis. Despite the high therapeutic efficacy of 5-FU in treatment of colorectal cancer, it is associated with undesired cardiac toxicities including coronary spasms, toxic inflammation and takotsubo cardiomyopathy. However, our patient did not fulfil the diagnostic criteria for the aforementioned complications. Based on this case report, we discuss alternative mechanisms including myocardial adenosine triphosphate depletion suggested from animal experiments.

Prognostic value of multi-detector computed tomography in asymptomatic aortic valve stenosis.

BACKGROUND: Multi-Detector Computed Tomography (MDCT) is a high-resolution imaging technique with potential additive value in the evaluation of patients with aortic valve stenosis (AS). We aimed to assess the prognostic value of MDCT in asymptomatic patients with AS compared to conventional transthoracic echocardiography (TTE). METHODS: 116 patients with asymptomatic AS (Vmax>2.5m/s assessed by clinical screening TTE, LVEF>50%) were examined with TTE (Vivid e9) and MDCT (Aquilion 320) on the same day. The treating physician was blinded for research protocol defined imaging results. Outcome was defined as indication for aortic valve replacement (AVR) determined by the treating physician or sudden cardiac death. RESULTS: The mean age was 72 (8) years, 27% were women, mean AVA by TTE was 1.01 (0.30) cm(2). Median follow up time was 27 (IQR 19-44) months. Forty seven patients (41%) developed indication for AVR. No patients suffered a sudden cardiac death. AVA and aortic valve calcification were significant univariable predictors of AVR when measured by both TTE and MDCT, whereas left ventricular mass was only significant measured by MDCT. Significant coronary artery disease by MDCT tended to predict future indication for AVR, but this did not reach statistical significance (HR: 1.79 (95% CI 0.96-3.44), p=0.08). CONCLUSION: MDCT derived AVA can be of use as an alternative to TTE derived AVA in patients with asymptomatic AS to predict future clinical indication for AVR.

Stroke in patients with aortic stenosis: the Simvastatin and Ezetimibe in Aortic Stenosis study.

BACKGROUND AND PURPOSE: There are limited data on risk stratification of stroke in aortic stenosis. This study examined predictors of stroke in aortic stenosis, the prognostic implications of stroke, and how aortic valve replacement (AVR) with or without concomitant coronary artery bypass grafting influenced the predicted outcomes. METHODS: Patients with mild-to-moderate aortic stenosis enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Diabetes mellitus, known atherosclerotic disease, and oral anticoagulation were exclusion criteria. Ischemic stroke was the primary end point, and poststroke survival a secondary outcome. Cox models treating AVR as a time-varying covariate were adjusted for atrial fibrillation and congestive heart failure, hypertension, age≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years and female sex (CHA2DS2-VASc) scores. RESULTS: One thousand five hundred nine patients were followed for 4.3±0.8 years (6529 patient-years). Rates of stroke were 5.6 versus 21.8 per 1000 patient-years pre- and post-AVR; 429 (28%) underwent AVR and 139 (9%) died. Atrial fibrillation (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.1-6.6), CHA2DS2-VASc score (HR 1.4 per unit; 95% CI, 1.1-1.8), diastolic blood pressure (HR, 1.4 per 10 mm Hg; 95% CI, 1.1-1.8), and AVR with concomitant coronary artery bypass grafting (HR, 3.2; 95% CI, 1.4-7.2, all P≤0.026) were independently associated with stroke. Incident stroke predicted death (HR, 8.1; 95% CI, 4.7-14.0; P<0.001). CONCLUSIONS: In patients with aortic stenosis not prescribed oral anticoagulation, atrial fibrillation, AVR with concomitant coronary artery bypass grafting, and CHA2DS2-VASc score were the major predictors of stroke. Incident stroke was strongly associated with mortality. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00092677.