Titration and Tolerability of Sacubitril/Valsartan for Patients With Heart Failure in Clinical Practice.

Little is known about the dosing and tolerability of sacubitril/valsartan (LCZ696; Entresto, Quebec, Canada) in a nonclinical trial population. This study was conducted to evaluate the use and tolerability of sacubitril/valsartan in patients followed at a multidisciplinary heart failure (HF) clinic. We performed a retrospective chart review of 126 patients with HF, initiated on sacubitril/valsartan, and seen at a specialty HF clinic between August 1, 2015, and August 1, 2017. We defined the target dose of sacubitril/valsartan as 200 mg twice a day. At baseline, median age was 67 years, 77% were men, median ejection fraction was 29%, and 86.5% of patients had symptoms of New York Heart Association class ≥II. Within 6 months of being transitioned onto sacubitril/valsartan therapy, 27.2% achieved the target dose of 200 mg twice a day, 40.8% achieved the target dose of 100 mg twice a day, and 32.0% achieved the target dose of 50 mg twice a day. The main reasons for not achieving target dose within 6 months included slower uptitration of therapy than in the trial (n = 41, 54.7%), a decrease in systolic blood pressure (n = 19, 25.3%), not completing blood work (n = 3, 4%), and patient noncompliance (n = 3, 4%). Overall, achievement of sacubitril/valsartan target doses was modest in a tertiary HF clinic, limited by various factors such as side effects and patients' medication noncompliance. Implementation of patient and clinician support pathways may improve uptake, uptitration, and maintenance of evidence-based doses in clinical practice.

Impact of contrast echocardiography on accurate discrimination of specific degree of left ventricular systolic dysfunction and comparison with cardiac magnetic resonance imaging.

AIM: Limited data exist on the impact of contrast-enhanced echocardiography on treatment decisions in heart failure patients that require specific left ventricular ejection fraction (LVEF) criteria. This study assessed accuracy of contrast-enhanced echocardiography in identifying patients with LVEF >35% vs ≤35% with cardiac magnetic resonance (CMR) used as reference method. METHODS AND RESULTS: Fifty-five patients from prospective Alberta HEART cohort with LVEF ≤50% on CMR were included. All patients had echocardiography performed within 2 weeks of CMR. Contrast agent was used when ≥2 contiguous LV endocardial segments were poorly visualized on echocardiography. LVEF was computed by Simpson's biplane method using non-contrast echocardiography and contrast-enhanced echocardiography and by outlining the endocardial contours in short-axis cine CMR images. Strong agreement in LV volumes and LVEF was seen between CMR and echocardiography with and without contrast (intra-class correlation coefficients >0.8) with less underestimation of LV volumes by contrast-enhanced echocardiography. Good agreement in LVEF ≤35% vs >35% was seen between CMR and non-contrast echocardiography with optimal images (κ 0.862) and contrast echocardiography (κ 0.769) while it was moderate for non-contrast echocardiography with suboptimal images (κ 0.491). The use of LV contrast in patients with suboptimal images (n = 39) resulted in correctly upgrading LVEF from ≤35% to >35% in 5 (13%) patients and downgrading LVEF from >35% to ≤35% in 2 (5%) patients using CMR as reference. CONCLUSIONS: Contrast-enhanced echocardiography in heart failure patients with suboptimal images helps to more accurately assess eligibility for specific therapies and avoid need for further testing, therefore should be considered routine part of echocardiographic assessment.

Anderson-Fabry cardiomyopathy: prevalence, pathophysiology, diagnosis and treatment.

Anderson-Fabry disease (AFD) is a lysosomal storage disease caused by the inappropriate accumulation of globotriaosylceramide in tissues due to a deficiency in the enzyme α-galactosidase A (α-Gal A). Anderson-Fabry cardiomyopathy is characterized by structural, valvular, vascular and conduction abnormalities, and is now the most common cause of mortality in patients with AFD. Large-scale metabolic and genetic screening studies have revealed AFD to be prevalent in populations of diverse ethnic origins, and the variant form of AFD represents an unrecognized health burden. Anderson-Fabry disease is an X-linked disorder, and genetic testing is critical for the diagnosis of AFD in women. Echocardiography with strain imaging and cardiac magnetic resonance imaging using late enhancement and T1 mapping are important imaging tools. The current therapy for AFD is enzyme replacement therapy (ERT), which can reverse or prevent AFD progression, while gene therapy and the use of molecular chaperones represent promising novel therapies for AFD. Anderson-Fabry cardiomyopathy is an important and potentially reversible cause of heart failure that involves LVH, increased susceptibility to arrhythmias and valvular regurgitation. Genetic testing and cardiac MRI are important diagnostic tools, and AFD cardiomyopathy is treatable if ERT is introduced early.

Prevalence and Prognostic Implications of Moderate or Severe Mitral Regurgitation in Patients with Bicuspid Aortic Valve.

BACKGROUND: Significant (moderate or greater) mitral regurgitation (MR) could augment the hemodynamic effects of aortic valvular disease in patients with bicuspid aortic valve (BAV), imposing a greater hemodynamic burden on the left ventricle and atrium, possibly culminating in a faster onset of left ventricular dilation and/or symptoms. The aim of this study was to determine the prevalence and prognostic implications of significant MR in patients with BAV. METHODS: In this large, multicenter, international registry, a total of 2,932 patients (mean age, 48 ± 18 years; 71% men) with BAV were identified. All patients were evaluated for the presence of significant primary or secondary MR by transthoracic echocardiography and were followed up for the end points of all-cause mortality and event-free survival. RESULTS: Overall, 147 patients (5.0%) had significant primary (1.5%) or secondary (3.5%) MR. Significant MR was associated with all-cause mortality (hazard ratio [HR], 2.80; 95% CI, 1.91-4.11; P < .001) and reduced event-free survival (HR, 1.97; 95% CI, 1.58-2.46; P < .001) on univariable analysis. MR was not associated with all-cause mortality (adjusted HR, 1.33; 95% CI, 0.85-2.07; P = .21) or event-free survival (adjusted HR, 1.10; 95% CI, 0.85-1.42; P = .49) after multivariable adjustment. However, sensitivity analyses demonstrated that significant MR not due to aortic valve disease retained an independent association with mortality (adjusted HR, 1.81; 95% CI, 1.04-3.15; P = .037). Subgroup analyses demonstrated an independent association between significant MR and all-cause mortality for individuals with significant aortic regurgitation (HR, 2.037; 95% CI, 1.025-4.049; P = .042), although this association was not observed for subgroups with significant aortic stenosis or without significant aortic valve dysfunction. CONCLUSIONS: Significant MR is uncommon in patients with BAV. Following adjustment for important confounding variables, significant MR was not associated with adverse prognosis in this large study of patients with BAV, except for the patient subgroup with moderate to severe aortic regurgitation. In addition, significant MR not due to aortic valve disease demonstrated an independent association with all-cause mortality.

Left ventricular remodelling in bicuspid aortic valve disease.

AIMS: Characterization of left ventricular (LV) geometric pattern and LV mass could provide an important insight into the pathophysiological adaptations of the LV to pressure and/or volume overload in patients with bicuspid aortic valve (BAV) and significant (≥moderate) aortic valve (AV) disease. This study aimed to characterize LV remodelling and its prognostic impact in patients with BAV according to the predominant type of valvular dysfunction. METHODS AND RESULTS: In this international, multicentre BAV registry, 1345 patients [51.0 (37.0-63.0) years, 71% male] with significant AV disease were identified. Patients were classified as having isolated aortic stenosis (AS) (n = 669), isolated aortic regurgitation (AR) (n = 499) or mixed aortic valve disease (MAVD) (n = 177). LV hypertrophy was defined as a LV mass index >115 g/m2 in males and >95 g/m2 in females. LV geometric pattern was classified as (i) normal geometry: no LV hypertrophy, relative wall thickness (RWT) ≤0.42, (ii) concentric remodelling: no LV hypertrophy, RWT >0.42, (iii) concentric hypertrophy: LV hypertrophy, RWT >0.42, and (iv) eccentric hypertrophy: LV hypertrophy, RWT ≤0.42. Patients were followed-up for the endpoints of event-free survival (defined as a composite of AV repair/replacement and all-cause mortality) and all-cause mortality. Type of AV dysfunction was related to significant variations in LV remodelling. Higher LV mass index, i.e. LV hypertrophy, was independently associated with the composite endpoint for patients with isolated AS [hazard ratio (HR) 1.08 per 25 g/m2, 95% confidence interval (CI) 1.00-1.17, P = 0.046] and AR (HR 1.19 per 25 g/m2, 95% CI 1.11-1.29, P < 0.001), but not for those with MAVD. The presence of concentric remodelling, concentric hypertrophy and eccentric hypertrophy were independently related to the composite endpoint in patients with isolated AS (HR 1.54, 95% CI 1.06-2.23, P = 0.024; HR 1.68, 95% CI 1.17-2.42, P = 0.005; HR 1.59, 95% CI 1.03-2.45, P = 0.038, respectively), while concentric hypertrophy and eccentric hypertrophy were independently associated with the combined endpoint for those with isolated AR (HR 2.49, 95% CI 1.35-4.60, P = 0.004 and HR 3.05, 95% CI 1.71-5.45, P < 0.001, respectively). There was no independent association observed between LV remodelling and the combined endpoint for patients with MAVD. CONCLUSIONS: LV hypertrophy or remodelling were independently associated with the composite endpoint of AV repair/replacement and all-cause mortality for patients with isolated AS and isolated AR, although not for patients with MAVD.

Impact of Left Ventricular Ejection Fraction on Clinical Outcomes in Bicuspid Aortic Valve Disease.

BACKGROUND: The prognostic impact of left ventricular ejection fraction (LVEF) in patients with bicuspid aortic valve (BAV) disease has not been previously studied. OBJECTIVES: The purpose of this study was to determine the prognostic impact of LVEF in BAV patients according to the type of aortic valve dysfunction. METHODS: We retrospectively analyzed the data collected in 2,672 patients included in an international registry of patients with BAV. Patients were classified according to the type of aortic valve dysfunction: isolated aortic stenosis (AS) (n = 749), isolated aortic regurgitation (AR) (n = 554), mixed aortic valve disease (MAVD) (n = 190), or no significant aortic valve dysfunction (n = 1,179; excluded from this analysis). The study population was divided according to LVEF strata to investigate its impact on clinical outcomes. RESULTS: The risk of all-cause mortality and the composite endpoint of aortic valve replacement or repair (AVR) and all-cause mortality increased when LVEF was <60% in the whole cohort as well as in the AS and AR groups, and when LVEF was <55% in MAVD group. In multivariable analysis, LVEF strata were significantly associated with increased rate of mortality (LVEF 50%-59%: HR: 1.83 [95% CI: 1.09-3.07]; P = 0.022; LVEF 30%-49%: HR: 1.97 [95% CI: 1.13-3.41]; P = 0.016; LVEF <30%: HR: 4.20 [95% CI: 2.01-8.75]; P < 0.001; vs LVEF 60%-70%, reference group). CONCLUSIONS: In BAV patients, the risk of adverse clinical outcomes increases significantly when the LVEF is <60%. These findings suggest that LVEF cutoff values proposed in the guidelines to indicate intervention should be raised from 50% to 60% in AS or AR and 55% in MAVD.

Prognostic implications of left atrial dilation in aortic regurgitation due to bicuspid aortic valve.

OBJECTIVE: To investigate the prognostic value of left atrial volume index (LAVI) in patients with moderate to severe aortic regurgitation (AR) and bicuspid aortic valve (BAV). METHODS: 554 individuals (45 (IQR 33-57) years, 80% male) with BAV and moderate or severe AR were selected from an international, multicentre registry. The association between LAVI and the combined endpoint of all-cause mortality or aortic valve surgery was investigated with Cox proportional hazard regression analyses. RESULTS: Dilated LAVI was observed in 181 (32.7%) patients. The mean indexed aortic annulus, sinus of Valsalva, sinotubular junction and ascending aorta diameters were 13.0±2.0 mm/m2, 19.4±3.7 mm/m2, 16.5±3.8 mm/m2 and 20.4±4.5 mm/m2, respectively. After a median follow-up of 23 (4-82) months, 272 patients underwent aortic valve surgery (89%) or died (11%). When compared with patients with normal LAVI (<35 mL/m2), those with a dilated LAVI (≥35 mL/m2) had significantly higher rates of aortic valve surgery or mortality (43% and 60% vs 23% and 36%, at 1 and 5 years of follow-up, respectively, p<0.001). Dilated LAVI was independently associated with reduced event-free survival (HR=1.450, 95% CI 1.085 to 1.938, p=0.012) after adjustment for LV ejection fraction, aortic root diameter, LV end-diastolic diameter and LV end-systolic diameter. CONCLUSIONS: In this large, multicentre registry of patients with BAV and moderate to severe AR, left atrial dilation was independently associated with reduced event-free survival. The role of this parameter for the risk stratification of individuals with significant AR merits further investigation.

Clinical and echocardiographic predictors of nonresponse to cardiac resynchronization therapy.

BACKGROUND: Lack of response to cardiac resynchronization therapy (CRT) ranges between 30% to 40% of heart failure (HF) patients. The present study aimed to evaluate the clinical and echocardiographic determinants of nonresponse to CRT. METHODS: A total of 581 patients (66.4 ± 10.0 years, 77.9% male) with advanced HF scheduled for CRT implantation were included. Clinical and echocardiographic evaluations were performed at baseline and 6 months of follow-up. Nonresponse was defined as no improvement in the New York Heart Association functional class, death from worsening HF or heart transplantation, and <15% reduction in left ventricular (LV) end-systolic volume. RESULTS: At 6 months of follow-up, 254 patients (44%) did not respond to CRT. The nonresponders were more frequently male (81.9% vs 74.3%, P = .030) and had ischemic cardiomyopathy (69.7% vs 53.2%, P < .001), shorter QRS duration (150.6 ± 29.9 milliseconds vs 156.0 ± 32.5 milliseconds, P = .041), worse New York Heart Association functional class (2.8 ± 0.6 vs 2.7 ± 0.6, P = .008) and shorter 6-minute walk distance (297.9 ± 110.7 m vs 331.8 ± 112.6 m, P = .001), larger left atrial volumes (44.9 ± 16.9 mL/m(2) vs 40.9 ± 17.6 mL/m(2), P = .006), less baseline LV dyssynchrony (56.2 ± 41.3 milliseconds vs 69.1 ± 39.9 milliseconds, P < .001), and, more frequently, anterior LV lead position (12.4% vs 4.0%, P = .007). At multivariate analysis, only the ischemic etiology of HF (odds ratio [OR] 2.264, P = .005), shorter 6-minute walk distance at baseline (OR 0.998, P = .030), less baseline LV dyssynchrony (OR 0.989, P < .001), and anterior LV lead position (OR 3.713, P < .010) remained independent predictors of nonresponse to CRT. CONCLUSIONS: Ischemic etiology of HF, shorter baseline 6-minute walk distance, less baseline LV dyssynchrony, and anterior LV lead position are independent determinants of nonresponse to CRT.

The incidence of stroke in patients with early echocardiography after acute myocardial infarction.

Left ventricular (LV) thrombus formation after ST-elevation myocardial infarction (STEMI) increases the risk of stroke. In our center, most echocardiograms are performed within 2 days post-STEMI. However, LV thrombi often become visible later. We assessed the 1-year incidence of stroke in patients without LV thrombus on echocardiography performed early (1-2 days) vs. later (day ≥ 3) post-STEMI. This retrospective observational study included 416 patients with acute STEMI. Patients with atrial fibrillation were excluded. All patients underwent echocardiography during admission. Patients with stroke within 12 months post-STEMI were identified from the hospital charts and administrative databases. Most echocardiograms (75%) were performed ≤ 2 days post-STEMI. LV thrombus was identified in 12 patients. One (8.3%) patient with LV thrombus and 10 (2.5%) patients without LV thrombus suffered stroke within 12 months post-STEMI. Most patients with stroke had apical akinesis. Most strokes occurred during the index admission or within 67 days of STEMI. There was no significant difference in the incidence of stroke between the patients with early vs. later echocardiography post-STEMI. The incidence of stroke after STEMI is low and similar between patients with echocardiography performed early vs. later post-STEMI which supports our current clinical practice. Importantly, most strokes occur in patients without LV thrombus on early echocardiography. High reported mortality rate associated with stroke following STEMI justifies the need for further validation in prospective studies to identify patients who may benefit from repeat imaging to detect later LV thrombus formation, and how this will impact patient outcomes and healthcare costs.

Multi-View 3-D Fusion Echocardiography: Enhancing Clinical Feasibility with a Novel Processing Technique.

A novel system for fusing 3-D echocardiography data sets from complementary acoustic windows was evaluated in 12 healthy volunteers and 12 patients with heart failure. We hypothesized that 3-D fusion would enable 3-D echocardiography in patients with limited acoustic windows. At least nine 3-D data sets were recorded, while three infrared cameras tracked the position and orientation of the transducer and chest respiratory movements. Corresponding 2-D planes of the fused 3-D data sets and of single-view 3-D data sets were assessed for image quality and compared with measurements of left ventricular function obtained with contrast 2-D echocardiography. The signal-to-noise ratio in accurately fused 3-D echocardiography recordings improved by 55% in systole (p < 0.001) and 47% in diastole (p < 0.00001) compared with the apical single-view recordings. The 3-D data sets acquired during short breath holds were successfully fused in 11 of 12 patients. The improvement in endocardial border definition (from 11.7 ± 6.0 to 24.0 ± 3.3, p < 0.01) enabled quantitative assessment of left ventricular function in 10 patients, with no significant difference in ejection fraction compared with contrast 2-D echocardiography. In patients with heart failure and limited acoustic windows, the novel fusion protocol provides 3-D data sets suitable for quantitative analysis of left ventricular function.

Longitudinal mechanics of the periinfarct zone and ventricular tachycardia inducibility in patients with chronic ischemic cardiomyopathy.

BACKGROUND: Quantification of segmental left ventricular (LV) strain by speckle-tracking echocardiography can identify transmural infarcts in patients with chronic ischemic cardiomyopathy. The aim of the study was to explore the relationship between the LV longitudinal peak systolic strain (LPSS) of the infarct, periinfarct, and remote zones and monomorphic ventricular tachycardia (VT) inducibility on electrophysiologic (EP) study. METHODS: A total of 134 patients with chronic ischemic cardiomyopathy scheduled for EP study were included. The protocol consisted of clinical, electrocardiographic, and echocardiographic evaluation, including LV longitudinal strain analysis using speckle-tracking echocardiography, immediately before EP study. An infarct segment was defined as a longitudinal strain value of greater than -5%, and a periinfarct segment was defined as immediately adjacent to an infarct segment. RESULTS: The infarct zone had the most impaired longitudinal strain (-0.5% ± 3.0%), whereas the periinfarct and remote zones had more preserved longitudinal strain (-10.8% ± 1.9% and -14.5% ± 3.0%, respectively; analysis of variance, P < .001). Seventy-two (54%) patients had inducible monomorphic VT on EP study. There was no significant difference in LV ejection fraction (31% ± 9% vs 32% ± 11%, P = .29) between inducible and noninducible patients. Longitudinal peak systolic strain of the periinfarct zone was more impaired in inducible patients (-9.8% ± 1.5% vs -11.0% ± 2.1%, P = .001), but no differences in LPSS of the infarct (-0.5% ± 3.2% vs -0.4% ± 2.7%, P = .75) and remote (-14.6% ± 2.8% vs -14.5% ± 3.4%, P = .92) zones were observed. Only LPSS of the periinfarct zone (OR 1.43, 95% CI 1.15-1.78, P = .001) was independently related to monomorphic VT inducibility on multiple logistic regression. CONCLUSIONS: Longitudinal strain analysis may be a useful imaging tool to risk stratify ischemic patients for malignant ventricular arrhythmia.

Prevalence and characteristics of patients with clinical improvement but not significant left ventricular reverse remodeling after cardiac resynchronization therapy.

BACKGROUND: Although most patients who improve in clinical status after cardiac resynchronization therapy (CRT) also show a significant left ventricular (LV) reverse remodeling, some patients do not show echocardiographic improvement. The aim of the present study was to evaluate the degree of agreement between clinical and echocardiographic response to CRT in a large cohort of heart failure patients, and to evaluate the characteristics of patients with clinical response but without echocardiographic response. METHODS: In 440 consecutive heart failure patients (mean age 66 ± 11 years, 81% men) treated with CRT, agreement between clinical and echocardiographic responses at 6 months of follow-up were evaluated. The combined clinical response was defined as: ≥1-point New York Heart Association functional class improvement or ≥15% increase in 6-minute walk test. Echocardiographic response was defined by a reduction in LV end-systolic volume (LVESV) ≥15%. RESULTS: At 6 months of follow-up, clinical response was observed in 84% (n = 370) of the patients. Significant reduction in LVESV was noted in 63% (n = 276). The majority of patients who improved clinically did show LV reverse remodeling (72%, n = 268). Importantly, 28% (n = 102) of patients who improved clinically did not show significant LV reverse remodeling. The patients with clinical response but without echocardiographic response had more often ischemic heart failure as compared to patients with positive clinical and echocardiographic response (69.6% vs 57.5%; P = .021). Moreover, patients with such discordant responses had more narrow QRS complex (148 ± 31 vs 159 ± 31 milliseconds; P = .004), and showed less LV dyssynchrony than patients with concordant positive responses (90 ± 77 vs 171 ± 105 milliseconds; P < .001). CONCLUSIONS: Although there is a good concordance between echocardiographic and clinical response to CRT, up to 28% of the population experienced clinical response without significant LV reverse remodeling. Subjects with such discrepant responses have more frequently ischemic heart failure and show more narrow QRS complex and less LV dyssynchrony than patients with both clinical and echocardiographic response.

Effects of Transcatheter Aortic Valve Implantation on Frailty and Quality of Life.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an effective alternative to surgical valve replacement in high-risk patients with severe aortic stenosis. Although measures of frailty have been used to attempt to predict outcomes in this population, few studies have demonstrated changes in these measures. METHODS: We performed a prospective, observational study of 171 patients undergoing TAVI, of whom 44 had maximal follow-up of 1 month and 50 had maximal follow-up of 1 year. Quality of life was assessed using the Minnesota Living With Heart Failure Questionnaire, Katz Index of Independence in Activities of Daily Living questionnaire, and patient perception of overall well-being. Frailty was measured using the 10-m walk test and handgrip strength testing. RESULTS: In the overall cohort, participants demonstrated improvements in quality of life metrics, but deterioration in 10-m walk test and handgrip at 1 month. These trends continued at 1 year. However, patients in the lowest quintile of handgrip and 10-m walk test demonstrated a trend of improvements in these metrics during follow-up. CONCLUSIONS: Despite improvements in quality of life after TAVI, no improvements in frailty were observed in patients at 1 year.

CONTEXTE: Le remplacement valvulaire aortique par cathéter (TAVI) est une solution de rechange efficace à la chirurgie de remplacement valvulaire chez les patients atteints de sténose aortique grave et présentant un risque élevé. Les mesures de la fragilité sont utilisées pour tenter de prévoir les résultats au sein de cette population. Néanmoins, peu d'études ont permis d'objectiver les variations de ces mesures. MÉTHODOLOGIE: Nous avons réalisé une étude observationnelle prospective portant sur 171 patients ayant subi un TAVI, dont 44 suivis pendant un mois ou moins, et 50 durant un an ou moins. La qualité de vie a été évaluée au moyen de questionnaires ­ Minnesota Living With Heart Failure Questionnaire et Katz Index of Independence in Activities of Daily Living Questionnaire ­ et en fonction de la perception du patient relativement à son bien-être général. La fragilité a été mesurée à l'aide d'un test de marche sur dix mètres et d'un test de force de préhension. RÉSULTATS: Dans l'ensemble de la cohorte, une amélioration des mesures de la qualité de vie a été observée parallèlement à une détérioration des résultats au test de marche sur dix mètres et au test de force de préhension après un mois. Les tendances à cet égard se sont poursuivies au bout d'un an. Cependant, les résultats des patients du quintile inférieur au test de marche sur 10 m et au test de force de préhension ont eu tendance à s'améliorer au cours de la période de suivi. CONCLUSIONS: Malgré une amélioration de la qualité de vie après le TAVI, la fragilité des patients ne s'est nullement améliorée après un an.

Cardiac involvement in critically ill patients with leptospirosis: A prospective study using myocardial deformation imaging.

BACKGROUND: Myocardial inflammation often complicates leptospirosis, a re-emerging global zoonosis. Leptospirosis associated myocardial dysfunction is equivocal and the pattern of cardiac involvement may not differ from that of sepsis associated myocarditis. METHODS: We prospectively compared cardiac involvement in 113 intensive care unit patients with severe leptospirosis to 31 patients with sepsis syndrome using a comprehensive assessment comprising of clinical presentation, electrocardiography, two-dimensional echocardiography (with global longitudinal strain calculation), and cardiac biomarker evaluation. Binomial logistic regression was performed to identify independent predictors of left ventricular systolic dysfunction in leptospirosis. RESULTS: Compared to sepsis syndrome, leptospirosis patients were younger, had higher body mass index measurements and were more likely to be smokers. Electrocardiography abnormalities were common and similar in both groups. Myocardial systolic dysfunction was common in both groups (leptospirosis: 55.86% vs sepsis syndrome: 51.61%, p=0.675) with subclinical left ventricular systolic dysfunction (characterized by abnormal global longitudinal strain and normal left ventricular ejection fraction) being most frequent followed by isolated right ventricular systolic dysfunction, isolated left ventricular systolic dysfunction, and bi-ventricular systolic dysfunction (leptospirosis: 31.43%, 18.42%, 13.16%, 10.53%, respectively; sepsis syndrome: 22.22%, 12.00%, 12.00%, 8.00%, respectively (p>0.05 for each comparator)). Leptospirosis patients had a trend towards greater troponin-T elevation (61.0% vs 40.0%, p=0.057). ST-segment elevation and elevated troponin were independent predictors of reduced left ventricular ejection fraction in leptospirosis. CONCLUSIONS: Cardiac involvement in leptospirosis appears to be similar to that of sepsis syndrome, with myocardial systolic dysfunction being common. As such, clinical vigilance pertaining to cardiac status is paramount in these high-risk patients.

Prognostic implications of left ventricular global longitudinal strain in patients with bicuspid aortic valve disease and preserved left ventricular ejection fraction.

AIMS: In patients with bicuspid aortic valve (BAV) and preserved left ventricular (LV) ejection fraction (EF), the frequency of impaired LV global longitudinal strain (GLS) and its prognostic implications are unknown. The present study evaluated the proportion and prognostic value of impaired LV GLS in patients with BAV and preserved LVEF. METHODS AND RESULTS: Five hundred and thirteen patients (68% men; mean age 44 ± 18 years) with BAV and preserved LVEF (>50%) were divided into five groups according to the type of BAV dysfunction: (i) normal function BAV, (ii) mild aortic stenosis (AS) or aortic regurgitation (AR), (iii) ≥moderate isolated AS, (iv) ≥moderate isolated AR, and (v) ≥moderate mixed AS and AR. LV systolic dysfunction based on 2D speckle-tracking echocardiography was defined as a cut-off value of LVGLS (-13.6%). The primary outcome was aortic valve intervention or all-cause mortality. The proportion of patients with LVGLS ≤-13.6% was the highest in the normal BAV group (97%) and the lowest in the group with moderate and severe mixed AS and AR (79%). During a median follow-up of 10 years, 210 (41%) patients underwent aortic valve replacement and 17 (3%) died. Patients with preserved LV systolic function (LVGLS ≤ -13.6%) had significantly better event-free survival compared to those with impaired LV systolic function (LVGLS > -13.6%). LVGLS was independently associated with increased risk of events (mainly aortic valve replacement): hazard ratio 1.09; P < 0.001. CONCLUSION: Impaired LVGLS in BAV with preserved LVEF is not infrequent and was independently associated with increased risk of events (mainly aortic valve replacement events).

Success Begins With Failure: An Alternative Approach in Transfemoral Transcatheter Aortic Valve Replacement Using an Antegrade Wire Crossing Technique.

Transcatheter aortic valve replacement has transitioned from an experimental procedure to an important alternative therapy for patients with symptomatic aortic stenosis and high surgical risk. We present a case outlining an approach to deal with the issue of "failure to cross" the aortic valve in transcatheter aortic valve replacement from the transfemoral retrograde approach.

Le remplacement valvulaire aortique par cathéter est passé d'une intervention expérimentale à un traitement alternatif important pour les patients atteints d'une sténose aortique symptomatique et exposés à un risque opératoire élevé. Nous présentons un cas qui décrit une approche pour remédier au problème d'« échec à traverser ¼ la valvule aortique lors du remplacement valvulaire aortique par cathéter selon une approche par voie rétrograde fémorale.

Resistant Hypertension From Renal Artery Stenosis Leading to Heart Failure With Preserved Ejection Fraction.

Resistant hypertension remains an important cause of heart failure. In this article, we describe a case of resistant hypertension in a 63-year-old woman leading to heart failure and marked morbidity. Her clinical course was characterized by chronic pleural effusions and recurrent hospitalizations with respiratory failure and flash pulmonary edema associated with heart failure with preserved ejection fraction. Her transthoracic echocardiogram showed severe concentric left hypertrophy and diastolic dysfunction. The clinical phenotype was secondary to resistant hypertension due to bilateral renal artery stenosis, and her blood pressure and heart failure resolved after successful renal artery angioplasty. This case demonstrates how heart failure with preserved ejection fraction due to renal artery stenosis can easily go unrecognized especially in patients with multiple comorbidities. The potentially curable nature of this condition clearly warrants consideration especially in patients with multiple risk factors for atherosclerotic vascular disease.

Transcatheter Mitral Valve Intervention for Chronic Mitral Regurgitation: A Plethora of Different Technologies.

Chronic mitral regurgitation (MR) remains a common cardiovascular condition resulting in significant morbidity and mortality. With an aging population, increasing trends for both primary (degenerative) and secondary (functional) MR have become apparent. Although the gold standard remains surgical intervention with mitral valve repair/replacement, comorbid conditions have steered the development of less invasive technologies to mitigate perioperative surgical risk. Transcatheter mitral valve repair using a percutaneous edge-to-edge technique is the most widely available choice at present. However, other transcatheter mitral valve repair techniques such as annuloplasty and chordal implantation are notable alternatives. Moreover, emerging technologies in transcatheter mitral valve replacement are rapidly establishing their roles in the field of chronic severe MR therapy. Hence, it is imperative to understand the indications and limitations of these various transcatheter mitral valve interventions to provide the best and most up-to-date clinical care for patients. This review will outline current evidence and patient selection criteria for such device-based therapies.

Sex Differences in Phenotypes of Bicuspid Aortic Valve and Aortopathy: Insights From a Large Multicenter, International Registry.

BACKGROUND: This large multicenter, international bicuspid aortic valve (BAV) registry aimed to define the sex differences in prevalence, valve morphology, dysfunction (aortic stenosis/regurgitation), aortopathy, and complications (endocarditis and aortic dissection). METHODS AND RESULTS: Demographic, clinical, and echocardiographic data at first presentation of 1992 patients with BAV (71.5% men) were retrospectively analyzed. BAV morphology and valve function were assessed; aortopathy configuration was defined as isolated dilatation of the sinus of Valsalva or sinotubular junction, isolated dilatation of the ascending aorta distal to the sinotubular junction, or diffuse dilatation of the aortic root and ascending aorta. New cases of endocarditis and aortic dissection were recorded. There were no significant sex differences regarding BAV morphology and frequency of normal valve function. When presenting with moderate/severe aortic valve dysfunction, men had more frequent aortic regurgitation than women (33.8% versus 22.2%, P<0.001), whereas women were more likely to have aortic stenosis (34.5% versus 44.1%, P<0.001). Men had more frequently isolated dilatation of the sinus of Valsalva or sinotubular junction (14.2% versus 6.7%, P<0.001) and diffuse dilatation of the aortic root and ascending aorta (16.2% versus 7.3%, P<0.001) than women. Endocarditis (4.5% versus 2.5%, P=0.037) and aortic dissections (0.5% versus 0%, P<0.001) occurred more frequently in men. CONCLUSIONS: Although there is a male predominance among patients with BAV, men with BAV had more frequently moderate/severe aortic regurgitation at first presentation compared with women, whereas women presented more often with moderate/severe aortic stenosis compared with men. Furthermore, men had more frequent aortopathy than women.

Prognostic Implications of Raphe in Bicuspid Aortic Valve Anatomy.

Importance: Little is known about the association between bicuspid aortic valve (BAV) morphologic findings and the degree of valvular dysfunction, presence of aortopathy, and complications, including aortic valve surgery, aortic dissection, and all-cause mortality. Objective: To investigate the association between BAV morphologic findings (raphe vs nonraphe) and the degree of valve dysfunction, presence of aortopathy, and prognosis (including need for aortic valve surgery, aortic dissection, and all-cause mortality). Design, Setting, and Participants: In this large international multicenter registry of patients with BAV treated at tertiary referral centers, 2118 patients with BAV were evaluated. Patients referred for echocardiography from June 1, 1991, through November 31, 2015, were included in the study. Exposures: Clinical and echocardiographic data were analyzed retrospectively. The morphologic BAV findings were categorized according to the Sievers and Schmidtke classification. Aortic valve function was divided into normal, regurgitation, or stenosis. Patterns of BAV aortopathy included the following: type 1, dilation of the ascending aorta and aortic root; type 2, isolated dilation of the ascending aorta; and type 3, isolated dilation of the sinus of Valsalva and/or sinotubular junction. Main Outcomes and Measures: Association between the presence and location of raphe and the risk of significant (moderate and severe) aortic valve dysfunction and aortic dilation and/or dissection. Results: Of the 2118 patients (mean [SD] age, 47 [18] years; 1525 [72.0%] male), 1881 (88.8%) had BAV with fusion raphe, whereas 237 (11.2%) had BAV without raphe. Bicuspid aortic valves with raphe had a significantly higher prevalence of valve dysfunction, with a significantly higher frequency of aortic regurgitation (622 [33.1%] vs 57 [24.1%], P < .001) and aortic stenosis (728 [38.7%] vs 51 [21.5%], P < .001). Furthermore, aortic valve replacement event rates were significantly higher among patients with BAV with raphe (364 [19.9%] at 1 year, 393 [21.4%] at 2 years, and 447 [24.4%] at 5 years) vs patients without raphe (30 [14.0%] at 1 year, 32 [15.0%] at 2 years, and 40 [18.0%] at 5 years) (P = .02). In addition, the all-cause mortality event rates were significantly higher among patients with BAV with raphe (77 [5.1%] at 1 year, 87 [6.2%] at 2 years, and 110 [9.5%] at 5 years) vs patients without raphe (2 [1.8%] at 1 year, 3 [3.0%] at 2 years, and 5 [4.4%] at 5 years) (P = .03). However, on multivariable analysis, the presence of raphe was not significantly associated with all-cause mortality. Conclusions and Relevance: In this large multicenter, international BAV registry, the presence of raphe was associated with a higher prevalence of significant aortic stenosis and regurgitation. The presence of raphe was also associated with increased rates of aortic valve and aortic surgery. Although patients with BAV and raphe had higher mortality rates than patients without, the presence of a raphe was not independently associated with increased all-cause mortality.