Resting Left Ventricular Global Longitudinal Strain to Identify Silent Myocardial Ischemia in Asymptomatic Patients with Diabetes Mellitus.

BACKGROUND: Screening for silent coronary artery disease in asymptomatic patients with diabetes mellitus (DM) is challenging and controversial. In this context, it seems crucial to identify early markers of coronary artery disease. METHODS: The aim of this study was to investigate the incremental value of resting left ventricular (LV) global longitudinal strain (GLS) for the prediction of positive results on stress (exercise or dobutamine) transthoracic echocardiography in 273 consecutive asymptomatic high-risk patients with DM. Positive results on stress transthoracic echocardiography were defined as stress-induced LV wall motion abnormalities (new or worsening preexisting abnormalities). RESULTS: Compared with patients with negative stress results, those with positive stress results (n = 28 [10%]) more frequently had cardiovascular risk factors, complications of DM, vascular disease, moderate and severe calcification of the aortic valve and mitral annulus, and worse resting LV GLS (-16.7 ± 2.9% vs -19.0 ± 1.9%, P < .001). On multivariable logistic regression analysis, DM duration > 10 years, diabetic retinopathy, LV hypertrophy, and impaired LV GLS (odds ratio, 1.39 [95% CI, 1.14-1.70] per percentage increase; odds ratio, 5.16 [95% CI, 1.96-13.59] for LV GLS worse than -18%) were independently associated with positive results on stress transthoracic echocardiography. The area under the curve to predict positive results was 0.74 for LV GLS with a cutoff of -18.0% (sensitivity 68%, specificity 78%). The area under the curve of the multivariable model to predict test results was improved by the addition of LV GLS (P < .001), with a bias-corrected area under the curve after bootstrapping of 0.842 [95% CI, 0.753-0.893]. CONCLUSIONS: The present findings show that resting LV GLS is associated with the presence of silent ischemia and could be useful to better identify asymptomatic patients with DM who might benefit from coronary artery disease screening.

Excess Mortality and Undertreatment of Women With Severe Aortic Stenosis.

Background Although women represent half of the population burden of aortic stenosis (AS), little is known whether sex affects the presentation, management, and outcome of patients with AS. Methods and Results In a cohort of 2429 patients with severe AS (49.5% women) we aimed to evaluate 5-year excess mortality and performance of aortic valve replacement (AVR) stratified by sex. At presentation, women were older (P<0.001), with less comorbidities (P=0.030) and more often symptomatic (P=0.007) than men. Women had smaller aortic valve area (P<0.001) than men but similar mean transaortic pressure gradient (P=0.18). The 5-year survival was lower compared with expected survival, especially for women (62±2% versus 71% for women and 69±1% versus 71% for men). Despite longer life expectancy in women than men, women had lower 5-year survival than men (66±2% [expected-75%] versus 68±2% [expected-70%], P<0.001) after matching for age. Overall, 5-year AVR incidence was 79±2% for men versus 70±2% for women (P<0.001) with male sex being independently associated with more frequent early AVR performance (odds ratio, 1.49; 1.18-1.97). After age matching, women remained more often symptomatic (P=0.004) but also displayed lower AVR use (64.4% versus 69.1%; P=0.018). Conclusions Women with severe AS are diagnosed at later ages and have more symptoms than men. Despite prevalent symptoms, AVR is less often performed in women and 5-year excess mortality is noted in women versus men, even after age matching. These imbalances should be addressed to ensure that both sexes receive equivalent care for severe AS.

Normative Reference Values of Cardiac Output by Pulsed-Wave Doppler Echocardiography in Adults.

Cardiac output (CO) is routinely assessed by pulsed-wave Doppler echocardiography, yet reference values in adults are lacking. We aim to establish normative values of CO and cardiac index (CI) by pulsed-wave Doppler-echocardiography and to analyze their relation with gender and age in nonobese and obese adults. We included 4,040 adults (mean age: 55 years, 53% women, 950 obese [body mass index ≥30 kg/m²]) with normal blood pressure, no history of cardiovascular disease, and normal transthoracic echocardiography. Normative reference CO and CI values for were calculated in 3,090 nonobese patients by quantile regression. CO normal limits were lower in females than in males (lower limit: 3.3 vs 3.5 L/min, upper limit: 7.3 vs 8.2 L/min). CI normal limits were identical for both genders (lower limit: 1.9 L/min/m², upper limit: 4.3 L/min/m²). Although the relation of CO to age was weak and observed only in women, CI of both genders was not influenced by age. CO of obese patients was significantly greater than that of their nonobese counterparts. CI of obese patients was not influenced by age and gender and was not significantly different than that of nonobese patients (lower limit 1.8 L/min/m², upper limit 4.1 L/min/m² for both genders). In conclusion, in a large adult population we establish normative reference values for CO and CI measured by Doppler-echocardiography. CI is a remarkably stable parameter that is not influenced by age, gender, and body size and should be used to define low- and high-output states.

Basal Takotsubo syndrome with transient severe mitral regurgitation caused by drug use: a case report.

BACKGROUND: Takotsubo syndrome (TTS) is a reversible cardiomyopathy. Little is known regarding its basal form and possible complications. CASE SUMMARY: A 31-year-old woman with no medical history was hospitalized for attempted suicide by ingestion of cocaine, benzodiazepine, and methadone. Initially, the patient received intensive care for coma and bradypnoea. After naloxone administration, the neurological situation improved, but the patient developed acute pulmonary oedema. Transthoracic echocardiography (TTE) revealed left ventricular systolic dysfunction with the basal wall's akinesia associated with moderate to severe restrictive mitral regurgitation. Global longitudinal strain (GLS) was impaired mainly in the basal segments. A coronary computed tomography ruled out coronary artery disease. Symptoms improved quickly under diuretic treatment. Transthoracic echocardiography at Day 6 showed improved basal wall contraction, with a left ventricular ejection fraction (LVEF) of 50% and moderate mitral regurgitation. TTE at Day 30 confirmed the diagnosis of myocardial infarction with non-obstructive coronary arteries related to a basal TTS after complete recovery of the LVEF, normalization of the wall motion and GLS, and the absence of residual mitral regurgitation. DISCUSSION: We report a case of acute pulmonary oedema due to basal TTS complicated by severe transient mitral regurgitation associated with moderate left ventricular dysfunction. Measuring strain by speckle-tracking can be useful to diagnose and monitor this entity. The use of coronary computed tomography is informative in young patients to rule-out coronary artery disease.

Improvement of the Prognosis Assessment of Severe Tricuspid Regurgitation by the Use of a Five-Grade Classification of Severity.

It is well known that some patients present with "more than severe" tricuspid regurgitation (TR). We aimed to assess the prognosis of these very severe TR patients. We defined very severe TR using 3 simple echocardiographic parameters: a coaptation gap≥10mm, a laminar TR flow and a systolic reversal of the hepatic vein flow. We included 259 consecutive patients (76 ± 13 years; 46% men) with moderate-to-severe TR (n = 114) and severe TR (n = 145). The primary end point was the combination of hospitalisation for right heart failure (RHF) and cardiovascular mortality. Median follow-up was 24(7 to 47) months. In patients with severe TR, 52 (36%) met the definition of very severe TR. These patients were younger, had more history of RHF and were more frequently treated with loop diuretics than those with moderate-to-severe TR (all p < 0.001). Four-year event-free survival rates were 68 ± 5%, for moderate-to-severe TR, 48 ± 6% for severe TR and only 35 ± 7% for very-severe TR (p < 0.001). On multivariable analysis, after adjustment for outcome predictors including age, comorbidity, RHF, TR etiology, left and right ventricular dysfunction, and tricuspid valve surgery, patients with very severe TR had a worsened prognosis than those with moderate-to-severe TR (Adjusted Hazard Ratio [95% Confidence Interval] = 2.43 [1.18 to 5.53]; p = 0.002) and than those with severe TR (Adjusted Hazard Ratio [95% Confidence Interval] = 2.23 [1.06 to 5.56]; p = 0.015). In conclusion, very severe TR is frequent in patients with severe TR, corresponds to a more advanced stage of the disease and is associated with poor outcomes. Therefore, the use of a 5-grade classification of TR severity is justified in routine clinical practice. (ID-RCB: 2017-A03233-50).

Spondylodiscitis complicating infective endocarditis.

OBJECTIVE: The primary objective was to assess the characteristics and prognosis of pyogenic spondylodiscitis (PS) in patients with infective endocarditis (IE). The secondary objectives were to assess the factors associated with occurrence of PS. METHODS: Prospective case-control bi-centre study of 1755 patients with definite IE with (n=150) or without (n=1605) PS. Clinical, microbiological and prognostic variables were recorded. RESULTS: Patients with PS were older (mean age 69.7±18 vs 66.2±14; p=0.004) and had more arterial hypertension (48% vs 34.5%; p<0.001) and autoimmune disease (5% vs 2%; p=0.03) than patients without PS. The lumbar vertebrae were the most frequently involved (84 patients, 66%), especially L4-L5. Neurological symptoms were observed in 59% of patients. Enterococci and Streptococcus gallolyticus were more frequent (24% vs 12% and 24% vs 11%; p<0001, respectively) in the PS group. The diagnosis of PS was based on contrast-enhanced MRI in 92 patients, bone CT in 88 patients and 18F-FDG PET/CT in 56 patients. In-hospital (16% vs 13.5%, p=0.38) and 1-year (21% vs 22%, p=0.82) mortalities did not differ between patients with or without PS. CONCLUSIONS: PS is a frequent complication of IE (8.5% of IE), is observed in older hypertensive patients with enterococcal or S. gallolyticus IE, and has a similar prognosis than other forms of IE. Since PS is associated with specific management, multimodality imaging including MRI, CT and PET/CT should be used for early diagnosis of this complication of endocarditis.

Characteristics and Prognosis of Patients With Moderate Aortic Stenosis and Preserved Left Ventricular Ejection Fraction.

Background Moderate aortic stenosis ( MAS ) has not been extensively studied and characterized, as no published study has been specifically devoted to this condition. Methods and Results We aimed to describe the characteristics of patients with MAS and to evaluate their long-term survival compared with that of the general population. This study included 508 patients (mean±SD age, 75±11 years) with MAS (aortic valve area between 1 and 1.5 cm2; mean±SD aortic valve area, 1.2±0.15 cm2) and preserved left ventricular ejection fraction. Patients were mostly (86.4%) asymptomatic or minimally symptomatic, 78.3% had hypertension, 36.2% were diabetics, and 48.3% had dyslipidemia. Each patient with MAS was matched for the average survival (per year) of all patients of the same age and same sex from our region (Somme department, north of France). During follow-up (median 47 months), 113 patients (22.2%) underwent aortic valve replacement for severe AS. The mean±SD time between inclusion and surgery was 37±22 months. During follow-up, 255 patients (50.2%) died. The 6-year survival of patients with MAS was lower than the expected survival (53±2% versus 65%). In multivariate analysis, age (hazard ratio, 1.04 [95% CI, 1.02-1.05]; P<0.001), prior atrial fibrillation (hazard ratio, 1.35 [95% CI, 1.05-1.73]; P=0.019), and Charlson comorbidity index (hazard ratio, 1.11 [95% CI, 1.05-1.18]; P=0.002) were associated with increased mortality. Aortic valve replacement was associated with better survival (hazard ratio, 0.38 [95% CI, 0.27-0.54]; P<0.001). Conclusions The results of this study show that patients with MAS present many cardiovascular risk factors, a high rate of surgery during follow-up, and increased mortality compared with the general population mainly related to associated comorbidities. Patients with MAS should, therefore, be managed for their cardiovascular risk factors and comorbidities. They require close follow-up, especially when the aortic valve area is close to 1 cm2, as aortic valve replacement performed when patients transition to severe AS and develop indications for surgery during follow-up is associated with better survival.

Impact of Preoperative Left Ventricular Remodelling Patterns on Long-Term Outcome after Aortic Valve Replacement for Severe Aortic Stenosis.

OBJECTIVES: Four patterns of left ventricular (LV) geometry have been described in aortic stenosis (AS): normal geometry, concentric remodelling (LVCR), concentric hypertrophy (CH), and eccentric hypertrophy (EH). LVCR and CH are independently associated with an increased risk of mortality in patients with medically managed AS. No data are available on the impact of aortic valve replacement (AVR) on the negative prognostic implications of LV remodelling patterns. METHODS: This study evaluated the long-term postoperative prognostic value of preoperative LV patterns in a cohort of 779 patients (mean age 73 years) with severe AS and ejection fraction >50% undergoing AVR. RESULTS: Long-term postoperative all-cause and cardiovascular mortality in patients with LVCR (adjusted HR = 0.50 [0.17-1.45], p = 0.202, and 0.45 [0.10-2.15], p = 0.373, respectively), CH (adjusted HR = 0.98 [0.68-1.40], p = 0.915, and 1.25 [0.60-2.40], p = 0.556, respectively), or EH (adjusted HR = 1.02 [0.79-1.32], p = 0.870, and 1.18 [0.70-1.99], p = 0.537, respectively) were comparable to those of patients with normal LV geometry. CONCLUSIONS: Despite the negative prognostic impact of LVCR and CH observed in patients with medically managed AS, these LV remodelling patterns are not associated with excess mortality after AVR. Surgery should therefore be discussed in patients with LVCR or CH and severe AS to avoid the risk of increased mortality observed under conservative management.

Impact of pulmonary hypertension on long-term outcome in patients with severe aortic stenosis.

Aims: Pulmonary hypertension (PH) is common in severe symptomatic left-sided valvular disease, particularly in aging populations. Inconsistent results have been reported concerning the association between PH and adverse outcomes after aortic valve replacement for aortic stenosis (AS). We therefore retrospectively investigated the prognostic significance of PH using peak tricuspid regurgitation velocity (TRV), as defined by the current European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines, in a large cohort of patients with severe AS. Methods and results: One thousand and nineteen patients (541 men; mean age 74 ± 11 years) with severe AS (aortic valve area (AVA) <1 cm2 and/or indexed AVA <0.6 cm2/m2 of body surface area) and LV ejection fraction ≥50% were included. Patients were divided into three groups according to the level of their peak TRV at the time of enrolment: Group 1 (n = 695, 68%) when TRV was ≤2.8 m/s; Group 2 (n = 212, 21%) when TRV was between 2.9 m/s and 3.4 m/s and Group 3 (n = 112, 11%) when TRV was > 3.4 m/s. Median overall follow-up was 31 [6-182] months. On univariate analysis, overall mortality during follow-up was globally different between groups (P < 0.001). On multivariate analysis, Group 3 (TRV >3.4 m/s) exhibited significant excess mortality after adjustment for covariates of prognostic importance (P = 0.032) and after further adjustment for surgery (P = 0.012), using Group 1 as the reference group. Dividing the whole population into two groups with a 3.4 m/s TRV threshold, overall mortality during follow-up was higher in the PH group [hazard ratio (HR) 1.87; 95% confidence interval [1.37-2.56]; P < 0.001)]. On multivariate analysis, after covariate adjustment, including surgery, Group 3 exhibited major excess mortality (adjusted HR 1.46 [1.10-1.95], P = 0.009). Conclusion: This study demonstrates the negative impact of pulmonary pressure, as assessed by current ESC/ERS guidelines, on long-term outcome of patients with severe AS, irrespective of functional status, chronic obstructive pulmonary disease, AS severity and surgery. Baseline TRV should therefore be taken into account in the management of severe AS.

Risk Stratification of Severe Aortic Stenosis With Preserved Left Ventricular Ejection Fraction Using Peak Aortic Jet Velocity: An Outcome Study.

BACKGROUND: Current guidelines consider aortic valve replacement reasonable in asymptomatic patients with very severe aortic stenosis (AS); however, the definition of very severe AS based on peak aortic jet velocity (Vmax) remains unclear with a 5-m/s cutoff in US guidelines and 5.5 m/s in European guidelines. Because ≈20% of patients with severe AS and preserved left ventricular ejection fraction have Vmax in this range, we aimed to assess the relationship between Vmax and mortality and determine the best threshold to define very severe AS. METHODS AND RESULTS: A total of 1140 patients with severe AS (aortic valve area ≤1 cm2, Vmax ≥4 m/s) and preserved left ventricular ejection fraction were included. The population was divided into 4 groups according to Vmax (4-4.49, 4.5-4.99, 5-5.49, and ≥5.5 m/s). After adjustment for covariates (including surgery), there was no difference in all-cause mortality between Vmax 4 to 4.49 m/s and Vmax 4.5 to 4.99 m/s (P=0.64). Both Vmax 5 to 5.49 m/s and Vmax ≥5.5 m/s exhibited significant excess mortality compared with Vmax 4 to 4.49 m/s (adjusted hazard ratio=1.34 [1.18-1.52]; P<0.001, and 1.28 [1.16-1.41]; P<0.001, respectively). Mortality risk was similar for Vmax 5 to 5.49 m/s and Vmax ≥5.5 m/s (P=0.93). Compared with Vmax <5 m/s, patients with Vmax ≥5 m/s had greater mortality risk (adjusted hazard ratio=1.86 [1.55-2.54]; P<0.001), even in the subgroup of asymptomatic even in the subgroup of asymptomatic patients (adjusted hazard ratio=2.08 [1.25-3.46]; P=0.005). CONCLUSIONS: Our results demonstrate the strong relationship between Vmax and mortality in patients with severe AS and preserved left ventricular ejection fraction irrespective of symptoms. Vmax ≥5 m/s at the time of AS diagnosis identifies patients with very severe AS at high risk of death.

Outcome Implication of Aortic Valve Area Normalized to Body Size in Asymptomatic Aortic Stenosis.

BACKGROUND: Current guidelines define severe aortic stenosis in patients with aortic valve area normalized to body surface area (AVA/BSA) <0.6 cm2/m2; yet, this cutoff has never been validated. Moreover, it is not known whether AVA normalization to other body size indexes allows improved outcome prediction. We aim to test the value of AVA normalized to body size for outcome prediction in asymptomatic aortic stenosis. METHODS AND RESULTS: We included 289 patients with asymptomatic aortic stenosis, preserved ejection fraction, and AVA<1.3 cm2 at diagnosis. The outcome measure was the occurrence of aortic valve replacement or all-cause death or during follow-up. AVA was normalized to BSA, height, weight, and body mass index. For each normalized index, patients in the lowest tertile were at high risk of events whereas outcome was similar for the other tertiles. High risk of events was observed with AVA/BSA <0.4 cm2/m2 (adjusted hazard ratio [HR], 3.42 [2.09-5.60]), AVA/height <0.45 cm2/m (adjusted HR, 3.99 [2.42-6.60]), AVA/weight <0.01 cm2/kg (adjusted HR, 3.37 [2.07-5.49]), and AVA/body mass index <0.029 cm2/kg per meter square (adjusted HR, 3.23 [1.99-5.24]). Mortality risk was high with AVA/height <0.45 cm2/m (adjusted HR, 2.18 [1.28-3.71]), followed by AVA/BSA <0.40 cm2/m2 (adjusted HR, 1.84 [1.09-3.11]), AVA/weight <0.01 cm2/kg (adjusted HR, 1.78 [1.07-2.98]), and AVA/body mass index <0.029 cm2/kg per meter square (adjusted HR, 1.75 [1.04-2.93]). AVA/height showed better predictive performance than AVA/BSA with improved reclassification and better discrimination (net reclassification improvement: 0.33 versus 0.28; integrated discrimination improvement: 0.10 versus 0.08; C statistic: 0.67 versus 0.65), whereas AVA/weight and AVA/body mass index showed lower predictive capacity. CONCLUSIONS: Among AVA normalization methods, AVA/height <0.45 cm2/m followed by AVA/BSA <0.40 cm2/m2 seem as robust parameters for defining high risk in asymptomatic aortic stenosis. The prognostic value of AVA/height deserves future research.