The impact of transoesophageal echocardiography in elderly patients with infective endocarditis.

BACKGROUND: Infective endocarditis (IE) increasingly involves older patients. Geriatric status may influence diagnostic and therapeutic decisions. AIM: To describe transoesophageal echocardiography (TEE) use in elderly IE patients, and its impact on therapeutic management and mortality. METHODS: A multicentre prospective observational study (ELDERL-IE) included 120 patients aged ≥75 years with definite or possible IE: mean age 83.1±5.0; range 75-101 years; 56 females (46.7%). Patients had an initial comprehensive geriatric assessment, and 3-month and 1-year follow-up. Comparisons were made between patients who did or did not undergo TEE. RESULTS: Transthoracic echocardiography revealed IE-related abnormalities in 85 patients (70.8%). Only 77 patients (64.2%) had TEE. Patients without TEE were older (85.4±6.0 vs. 81.9±3.9 years; P=0.0011), had more comorbidities (Cumulative Illness Rating Scale-Geriatric score 17.9±7.8 vs. 12.8±6.7; P=0.0005), more often had no history of valvular disease (60.5% vs. 37.7%; P=0.0363), had a trend toward a higher Staphylococcus aureus infection rate (34.9% vs. 22.1%; P=0.13) and less often an abscess (4.7% vs. 22.1%; P=0.0122). Regarding the comprehensive geriatric assessment, patients without TEE had poorer functional, nutritional and cognitive statuses. Surgery was performed in 19 (15.8%) patients, all with TEE, was theoretically indicated but not performed in 15 (19.5%) patients with and 6 (14.0%) without TEE, and was not indicated in 43 (55.8%) patients with and 37 (86.0%) without TEE (P=0.0006). Mortality was significantly higher in patients without TEE. CONCLUSIONS: Despite similar IE features, surgical indication was less frequently recognized in patients without TEE, who less often had surgery and had a poorer prognosis. Cardiac lesions might have been underdiagnosed in the absence of TEE, hampering optimal therapeutic management. Advice of geriatricians should help cardiologists to better use TEE in elderly patients with suspected IE.

Extent of Low-density Lipoprotein Cholesterol Reduction and All-cause and Cardiovascular Mortality Benefit: A Systematic Review and Meta-analysis.

ABSTRACT: Lipid-modifying agents steadily lower low-density lipoprotein cholesterol (LDL-C) levels with the aim of reducing mortality. A systematic review and meta-analysis were conducted to determine whether all-cause or cardiovascular (CV) mortality effect size for lipid-lowering therapy varied according to the magnitude of LDL-C reduction. Electronic databases were searched, including PubMed and ClinicalTrials.gov , from inception to December 31, 2019. Eligible studies included randomized controlled trials that compared lipid-modifying agents (statins, ezetimibe, and PCSK-9 inhibitors) versus placebo, standard or usual care or intensive versus less-intensive LDL-C-lowering therapy in adults, with or without known history of CV disease with a follow-up of at least 52 weeks. All-cause and CV mortality as primary end points, myocardial infarction, stroke, and non-CV death as secondary end points. Absolute risk differences [ARD (ARDs) expressed as incident events per 1000 person-years], number needed to treat (NNT), and rate ratios (RR) were assessed. Sixty randomized controlled trials totaling 323,950 participants were included. Compared with placebo, usual care or less-intensive therapy, active or more potent lipid-lowering therapy reduced the risk of all-cause death [ARD -1.33 (-1.89 to -0.76); NNT 754 (529-1309); RR 0.92 (0.89-0.96)]. Intensive LDL-C percent lowering was not associated with further reductions in all-cause mortality [ARD -0.27 (-1.24 to 0.71); RR 1.00 (0.94-1.06)]. Intensive LDL-C percent lowering did not further reduce CV mortality [ARD -0.28 (-0.83 to 0.38); RR 1.02 (0.94-1.09)]. Our findings indicate that risk reduction varies across subgroups and that overall NNTs are high. Identifying patient subgroups who benefit the most from LDL-C levels reduction is clinically relevant and necessary.

Vasoplegic Syndrome after Cardiac Surgery for Infective Endocarditis.

Purpose: Post-operative vasoplegic syndrome is a dreaded complication in infective endocarditis (IE). Methods and Results: This retrospective study included 166 consecutive patients referred to cardiac surgery for non-shocked IE. Post-operative vasoplegic syndrome was defined as a persistent hypotension (mean blood pressure < 65 mmHg) refractory to fluid loading and cardiac output restoration. Cardiac surgery was performed 7 (5−12) days after the beginning of antibiotic treatment, 4 (1−9) days after negative blood culture and in 72.3% patients with adapted anti-biotherapy. Timing of cardiac surgery was based on ESC guidelines and operating room availability. Most patients required valve replacement (80%) and cardiopulmonary bypass (CPB) duration was 106 (95−184) min. Multivalvular surgery was performed in 43 patients, 32 had tricuspid valve surgery. Post-operative vasoplegic syndrome was reported in 53/166 patients (31.9%, 95% confidence interval of 24.8−39.0%) of the whole population; only 15.1% (n = 8) of vasoplegic patients had a post-operative documented infection (6 positive blood cultures) and no difference was reported between vasoplegic and non-vasoplegic patients for valve culture and the timing of cardiac surgery. Of the 23 (13.8%) in hospital-deaths, 87.0% (n = 20) occurred in the vasoplegic group and the main causes of death were multiorgan failure (n = 17) and neurological complications (n = 3). Variables independently associated with vasoplegic syndrome were CPB duration (1.82 (1.16−2.88) per tertile) and NTproBNP level (2.11 (1.35−3.30) per tertile). Conclusions: Post-operative vasoplegic syndrome is frequent and is the main cause of death after IE cardiac surgery. Our data suggested that the mechanism of vasoplegic syndrome was more related to inflammatory cardiovascular injury rather than the consequence of ongoing bacteremia.

Cardiovascular Disease Risk Reduction and Body Mass Index.

PURPOSE OF REVIEW: Anti-hypertensive and lipid lowering therapy addresses only half of the cardiovascular disease risk in patients with body mass index > 30 kg/m2, i.e., obesity. We examine newer aspects of obesity pathobiology that underlie the partial effectiveness of anti-hypertensive lipid lowering therapy for the reduction of cardiovascular disease risk in obesity. RECENT FINDINGS: Obesity-related insulin resistance, vascular endothelium dysfunction, increased sympathetic nervous system/renin-angiotensin-aldosterone system activity, and glomerulopathy lead to type 2 diabetes, coronary atherosclerosis, and chronic disease kidney disease that besides hypertension and dyslipidemia increase cardiovascular disease risk. Obesity increases cardiovascular disease risk through multiple pathways. Optimal reduction of cardiovascular disease risk in patients with obesity is likely to require therapy targeted at both obesity and obesity-associated conditions.

Cardiac valvular surgery and history of anorectic drug intake: A retrospective study of a large population of benfluorex-exposed patients.

BACKGROUND: Anorectic drugs are overlooked as a cause of valvular heart disease (VHD). AIM: To describe the characteristics of a large population of patients with severe VHD who underwent cardiac surgery and had a history of benfluorex intake. METHODS: Retrospective observational and cross-sectional study of patients from a large French database (Office National d'Indemnisation des Accidents Médicaux). Clinical, echocardiographic, surgical and pathology findings were comprehensively collected from medical files. RESULTS: From a chart review of 9584 subjects, 1031 patients with VHD underwent cardiac surgery; 453 surgical patients were excluded because of VHD obviously unrelated to benfluorex exposure, six because of missing data and eight declined to participate. The final study population comprised 564 patients who had surgery between 1987 and 2019. Median age was 58 (interquartile range 50-65) years; 85% were female. Median duration of preoperative benfluorex exposure was 5.8 (3.3-10) years. Most patients had aortic and mitral valve disease. Pure or predominant aortic and/or mitral regurgitation were found in 84% of patients (n=471), and aortic or mitral stenosis (pure or combined with regurgitation) in 12% (n=67) and 15% (n=84), respectively. Overall, 403 aortic, 402 mitral and 64 tricuspid valve surgical procedures were collected. Aortic and mitral valves were found to be thickened, rigid and/or restrictive in most cases; restrictive tricuspid valve disease was seldom documented. Pathology was available in half of the population (276 patients); valvular fibrosis suggestive of drug-induced VHD was found in 222 patients, including 146 with expert examination. Mixed VHD aetiologies were discussed in 107 patients, including 54 with available pathology. CONCLUSIONS: Drug-induced VHD features are miscellaneous, including well-known restrictive valvular regurgitation, but also stenosis or combined regurgitation and stenosis. Besides a history of drug taking, thorough echocardiography and comprehensive surgical reports, pathology is key in the diagnostic procedure.

An Exceedingly Rare Case of Concomitant Quadricuspid Aortic Valve and Atrial Myxoma.

We present an exceptional case of a quadricuspid aortic valve associated with a left atrial myxoma. Both are rare conditions, and this association has not been reported yet. These conditions can be silent but may lead to several complications. This case highlights importance of a careful echocardiographic evaluation for early management. (Level of Difficulty: Beginner.).

Clinical Significance of Global Wasted Work in Patients with Heart Failure Receiving Cardiac Resynchronization Therapy.

BACKGROUND: The relationship between myocardial work assessment using pressure-strain loops by echocardiography before cardiac resynchronization therapy (CRT) and response to CRT has been recently revealed. Among myocardial work parameters, the impact of left ventricular myocardial global wasted work (GWW) on response to CRT and outcome following CRT has been seldom studied. Hence, the authors evaluated the relationship between preprocedural GWW and outcome in a large prospective cohort of patients with heart failure (HF) and reduced ejection fraction receiving CRT. METHODS: The study included 249 patients with HF. Myocardial work indices including GWW were calculated using speckle-tracking strain two-dimensional echocardiography using pressure-strain loops. End points of the study were (1) response to CRT, defined as left ventricular reverse remodeling and/or absence of hospitalization for HF, and (2) all-cause death during follow-up. RESULTS: Median follow-up duration was 48 months (interquartile range, 43-54 months). Median preoperative GWW was 281 mm Hg% (interquartile range, 184-388 mm Hg%). Preoperative GWW was associated with CRT response (area under the curve, 0.74; P < .0001), and a 200 mm Hg% threshold discriminated CRT nonresponders from responders with 85% specificity and 50% sensitivity, even after adjustment for known predictors of CRT response (adjusted odds ratio, 4.03; 95% CI, 1.91-8.68; P < .001). After adjustment for established predictors of outcome in patients with HF with reduced ejection fraction receiving CRT, GWW < 200 mm Hg% remained associated with a relative increased risk for all-cause death compared with GWW ≥ 200 mm Hg% (adjusted hazard ratio, 2.0; 95% CI, 1.1-3.9; P = .0245). Adding GWW to a baseline model including known predictors of outcome in CRT resulted in an improvement of this model (χ2 to improve 4.85, P = .028). The relationship between GWW and CRT response and outcome was stronger in terms of size effect and statistical significance than for other myocardial work indices. CONCLUSIONS: Low preoperative GWW (<200 mm Hg%) is associated with absence of CRT response in CRT candidates and with a relative increased risk for all-cause death. GWW appears to be a promising parameter to improve selection for CRT of patients with HF with reduced ejection fraction.

Clinical and prognostic implications of phenomapping in patients with heart failure receiving cardiac resynchronization therapy.

BACKGROUND: Despite having an indication for cardiac resynchronization therapy according to current guidelines, patients with heart failure with reduced ejection fraction who receive cardiac resynchronization therapy do not consistently derive benefit from it. AIM: To determine whether unsupervised clustering analysis (phenomapping) can identify distinct phenogroups of patients with differential outcomes among cardiac resynchronization therapy recipients from routine clinical practice. METHODS: We used unsupervised hierarchical cluster analysis of phenotypic data after data reduction (55 clinical, biological and echocardiographic variables) to define new phenogroups among 328 patients with heart failure with reduced ejection fraction from routine clinical practice enrolled before cardiac resynchronization therapy. Clinical outcomes and cardiac resynchronization therapy response rate were studied according to phenogroups. RESULTS: Although all patients met the recommended criteria for cardiac resynchronization therapy implantation, phenomapping analysis classified study participants into four phenogroups that differed distinctively in clinical, biological, electrocardiographic and echocardiographic characteristics and outcomes. Patients from phenogroups 1 and 2 had the most improved outcome in terms of mortality, associated with cardiac resynchronization therapy response rates of 81% and 78%, respectively. In contrast, patients from phenogroups 3 and 4 had cardiac resynchronization therapy response rates of 39% and 59%, respectively, and the worst outcome, with a considerably increased risk of mortality compared with patients from phenogroup 1 (hazard ratio 3.23, 95% confidence interval 1.9-5.5 and hazard ratio 2.49, 95% confidence interval 1.38-4.50, respectively). CONCLUSIONS: Among patients with heart failure with reduced ejection fraction with an indication for cardiac resynchronization therapy from routine clinical practice, phenomapping identifies subgroups of patients with differential clinical, biological and echocardiographic features strongly linked to divergent outcomes and responses to cardiac resynchronization therapy. This approach may help to identify patients who will derive most benefit from cardiac resynchronization therapy in "individualized" clinical practice.

Watchful waiting care or early intervention in asymptomatic severe aortic stenosis: Where we are.

Aortic stenosis, the most common valvular heart disease in Western countries, affects predominantly older people. Prompt aortic valve replacement is undoubtedly indicated in symptomatic patients. Management of asymptomatic patients is nowadays shifting from a conservative approach to early aortic valve replacement, as multimodality imaging is increasingly available. However, multimodality imaging has led to multiple prognostic parameters and complex algorithms, as well as a new staging classification that has left patients and physicians somewhat puzzled. We highlight the value of thorough serial clinical examinations, Doppler echocardiography and exercise testing when caring for a growing aortic stenosis population, including that has no or limited access to multimodality imaging. Evidence for early aortic valve replacement versus conservative management in asymptomatic patients with severe aortic stenosis is biased by the lack of serial stress testing evaluation; 30% of so-called asymptomatic patients were in fact symptomatic, and thus were clear candidates for aortic valve replacement in the above-mentioned studies. Randomized trials of aortic valve replacement versus conservative management that include serial stress testing evaluation are needed to ascertain whether early aortic valve replacement actually improves clinical outcome in asymptomatic patients with severe aortic stenosis. Less interventional medicine and healthcare resource utilization can result in better health.

Dimensionless Index in Patients With Low-Gradient Severe Aortic Stenosis and Preserved Ejection Fraction.

Background Risk stratification of patients with low-gradient (LG) severe aortic stenosis (AS) despite preserved left ventricular ejection fraction remains challenging. We sought to evaluate the relationship between the dimensionless index (DI)-the ratio of the left ventricular outflow tract time-velocity integral to that of the aortic valve jet-and mortality in these patients. Methods Seven hundred fifty-five patients with LG severe AS (defined by aortic valve area ≤1 cm2 or aortic valve area indexed to body surface area ≤0.6 cm2/m2 and mean aortic pressure gradient <40 mm Hg) and preserved left ventricular ejection fraction ≥50% were studied. Flow status was defined according to stroke volume index <35 mL/m2 (low flow, LF) or ≥35 mL/m2 (normal flow, NF). Results After adjustment for age, sex, body mass index, Charlson comorbidity index, history of hypertension, history of atrial fibrillation, AS-related symptoms, left ventricular ejection fraction, indexed left ventricular ventricular mass, aortic valve area, and aortic valve replacement as a time-dependent covariate, patients with LG-LF and DI<0.25 exhibited a considerable increased risk of death compared with patients with LG-NF and DI≥0.25 (adjusted hazard ratio, 2.41 [95% CI, 1.61-3.62]; P<0.001), LG-NF and DI<0.25 (adjusted hazard ratio, 1.84 [95% CI, 1.24-2.73]; P=0.003), and LG-LF and D≥0.25 (adjusted hazard ratio, 2.27 [95% CI, 1.42-3.63]; P<0.001). In contrast, patients with LG-LF and DI≥0.25, LG-NF and DI<0.25, and LG-NF and DI≥0.25 had similar outcome. DI<0.25 showed incremental prognostic value in patients with LG-LF severe AS but not in patients with LG-NF severe AS. Conclusions Among patients with LG severe AS and preserved left ventricular ejection fraction, decreased DI<0.25 is a reliable parameter in patients with LF to identify a subgroup of patients at higher risk of death who may derive benefit from aortic valve replacement.

Prognostic Importance of Left Ventricular Global Longitudinal Strain in Patients with Severe Aortic Stenosis and Preserved Ejection Fraction.

BACKGROUND: Impaired left ventricular (LV) speckle-tracking-derived global longitudinal strain (GLS) magnitude (GLS worse than 14.7%) has been associated with poor outcome in patients with severe aortic stenosis (AS) and preserved LV ejection fraction (EF). OBJECTIVES: To test the hypothesis that GLS magnitude ≤ 15% obtained with vendor-independent speckle-tracking strain software may be able to identify patients with severe AS who are at higher risk of death, despite preserved LVEF and no or mild symptoms. METHODS: GLS was retrospectively obtained in 332 patients with severe AS (aortic valve area indexed [AVAi] < 0.6 cm2/m2), no or mild symptoms, and LVEF ≥ 50%. Absolute values of GLS were collected. Survival analyses were carried out to study the impact of GLS magnitude on all-cause mortality. RESULTS: During a median follow-up period of 42 (37-46) months, 105 patients died. On multivariate analysis, and after adjustment of known clinical and/or echocardiographic predictors of outcome and aortic valve replacement as a time-dependent covariate, GLS magnitude ≤ 15% was independently associated with mortality during follow-up (all P < .01). Adding GLS magnitude ≤ 15% (adjusted hazard ratio = 1.99 [1.17-3.38], P = .011) to a multivariate model including clinical and echocardiographic variables of prognostic importance (aortic valve replacement, aortic valve area, LV stroke volume index < 30 mL/m2, and LVEF<60%) improved the predictive performance with improved global model fit, reclassification, and better discrimination. After propensity score matching (n = 196), increased risk of mortality persisted among patients with GLS magnitude ≤ 15% compared with those with GLS > 15% (hazard ratio = 2.10; 95% confidence interval, 1.20-3.68; P = .009). CONCLUSIONS: In this series of patients with severe AS, no or mild symptoms, and LVEF ≥ 50%, GLS obtained with vendor-independent speckle-tracking strain software was an effective tool to identify patients with a poor outcome. Detection of myocardial dysfunction by identifying GLS magnitude < 15% in patients with severe AS, no or mild symptoms, and LVEF ≥ 50%, can aid in risk assessment.