Prevalence and long-term outcome of aortic prosthesis-patient mismatch in patients with paradoxical low-flow severe aortic stenosis.

BACKGROUND: Patients with severe aortic stenosis (AS) and paradoxical low flow (PLF) have worse outcome compared with those with normal flow. Furthermore, prosthesis-patient mismatch (PPM) after aortic valve replacement is a predictor of reduced survival. However, the prevalence and prognostic impact of PPM in patients with PLF-AS are unknown. We aimed to analyze the prevalence and long-term survival of PPM in patients with PLF-AS. METHODS AND RESULTS: Between 2000 and 2010, 677 patients with severe AS, preserved left ventricular ejection fraction, and aortic valve replacement were included (74±8 years; 42% women; aortic valve area, 0.69±0.16 cm(2)). A PLF (indexed stroke volume ≤35 mL/m(2)) was found in 26%, and after aortic valve replacement, 54% of patients had PPM, defined as an indexed effective orifice area ≤0.85 cm(2)/m(2). The combined presence of PLF and PPM was found in 15%. Compared with patients with noPLF/noPPM, those with PLF/PPM were significantly older, with more comorbidities. They also received smaller and biological bioprosthesis more often (all P<0.01). Although early mortality was not significantly different between groups, the 10-year survival rate was significantly reduced in case of PLF/PPM compared with noPLF/noPPM (38±9% versus 70±5%; P=0.002), even after multivariable adjustment (hazard ratio, 2.58; 95% confidence interval, 1.5-4.45; P=0.0007). CONCLUSIONS: In this large catheterization-based study, the coexistence of PLF-AS before surgery and PPM after surgery is associated with the poorest outcome.

Outcome and impact of surgery in paradoxical low-flow, low-gradient severe aortic stenosis and preserved left ventricular ejection fraction: a cardiac catheterization study.

BACKGROUND: The clinical relevance and management of paradoxical low-flow, low-gradient aortic stenosis (LFLG-AS) with preserved left ventricular ejection fraction remain debated. The aim of this study is to determine the features and outcome of LFLG-AS assessed using cardiac catheterization. METHODS AND RESULTS: Between 2000 and 2010, 768 patients with preserved left ventricular ejection fraction (>50%) and severe AS (valve area ≤ 1 cm(2)) without other valvular disease underwent cardiac catheterization. Mean age was 74 ± 8 years, 42% were women, and 46% had associated coronary artery disease. The prevalence of LFLG (indexed left ventricular stroke volume <35 mL/m(2) and mean gradient <40 mm Hg), normal flow high gradient, normal flow low gradient, and low flow high gradient were 13%, 50%, 22%, and 15%, respectively. Compared with patients with normal flow high gradient, those with LFLG were significantly older, with significantly reduced systemic arterial compliance and vascular resistances and increased valvulo-arterial impedance (all P<0.05). Ten-year survival was reduced in LFLG-AS (32 ± 9%) compared with normal flow high gradient (66 ± 4%; P=0.0002). After adjustment for other risk factors, LFLG-AS was independently associated with reduced long-term survival (hazard ratio, 1.85; 95% confidence interval, 1.08-3.07; P=0.02). However, despite higher operative mortality, patients with LFLG-AS undergoing aortic valve replacement seemed to have better long-term survival than those managed conservatively (5-year survival rate: 63 ± 6% versus 38 ± 15%; P=0.007; hazard ratio, 0.23; 95% confidence interval, 0.09-0.59; P=0.002). CONCLUSIONS: This large cardiac catheterization-based study reports that the LFLG-AS entity is not rare and is associated with worse outcome whether treated medically or surgically. However, these patients may have better long-term survival if treated surgically. Further prospective studies are needed to confirm this finding.

Management and long-term outcomes of patients with chronic inflammatory diseases experiencing ST-segment elevation myocardial infarction: The SCALIM registry.

BACKGROUND: Patients with chronic inflammatory diseases (CIDs) are at increased risk of cardiovascular events. However, the prognostic impact of CID after an acute coronary event has been poorly studied. AIMS: To examine the effect of history of CID on long-term outcome in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: We analysed data from SCALIM, a regional registry that prospectively enrolled patients with STEMI between June 2011 and May 2019. The presence of CID (including inflammatory bowel diseases, rheumatic conditions, inflammatory skin diseases, multiple sclerosis, vasculitis and autoimmune diseases) was identified. The primary outcome was all-cause death. Secondary outcomes were cardiovascular death, myocardial infarction, ischaemic stroke, peripheral vascular events and rehospitalization for cardiovascular conditions. RESULTS: Data from 1941 patients with STEMI (mean age 64.8±14.1 years, 75.1% men) were analyzed. The prevalence of any CID was 4.6% (n=89). After a mean follow-up of 3.4±2.6 years, the overall death rate was 16.2%, with similar 5-year survival between patients with and without CID (74.2% vs. 81.9%, respectively; P=0.121), with no significant mortality excess (hazard ratio: 1.15, 95% confidence interval: 0.73-1.82; P=0.55). However, among CID patients, 35 (39.3%) were on corticosteroid therapy and showed decreased 5-year survival (52.8% vs. 89.5% without corticosteroids; P=0.001). We found no increased rate of secondary endpoints, except for peripheral vascular events (5-year survival free of peripheral events: 93.3% vs. 98.6% in those without CID; P=0.005). CONCLUSIONS: Approximately 1 in 20 patients with STEMI has CID. We found no effect of CID on long-term survival. However, patients on corticosteroid therapy appeared to have higher rates of death during follow-up. Whether this finding is related to the use of corticosteroids or to the more progressive nature of their condition warrants further investigation.

Characteristics associated with patient delay during the management of ST-segment elevated myocardial infarction, and the influence of awareness campaigns.

BACKGROUND: The delay between the occurrence of symptoms and the call seeking medical assistance is an important component of the pain-to-balloon delay in patients with ST-segment elevation myocardial infarction (STEMI). Factors affecting this "patient delay" have been poorly studied, and campaigns to raise emergency call awareness have barely been evaluated. AIMS: To evaluate the factors related to patient delay, and the effects of public awareness campaigns undertaken in our region. METHODS: Data from the regional registry of STEMI in Limousin, France, were analysed, and we performed a survey to assess medical history, clinical signs, context, socioeconomic situation and perception and behaviour of the patient. "Late callers" (i.e. third tertile,>154minutes) were compared with "early callers" (i.e. first and second tertiles,≤154minutes) using univariate and multivariable statistical methods. The influence of public awareness campaigns was studied by comparing the patient delays before and after a regional campaign. RESULTS: Among 481 patients, the median patient delay was 87minutes. "Late callers" were older (odds ratio [OR] 1.02 per year, 95% confidence interval [CI] 1.00 to 1.03), more often had symptom onset between 00:00 and 05:59 a.m. (OR 1.86, 95% CI 1.10 to 3.12) and more often sought assistance from a general practitioner (OR 2.58, 95% CI 1.66 to 4.04) or attended the emergency room (OR 4.10, 95% CI 2.04 to 8.32). Sweats and considering the situation to be severe were factors associated with a reduced delay. After awareness campaigns, there was no change in patient delay, but the proportion of patients calling the Emergency Medical Services increased from 55% to 62% (P<0.001). CONCLUSIONS: Patient delay is multifactorial. The impact of previous campaigns is mixed. Psychological and behavioural aspects are determinant, and should be taken into consideration to develop awareness messages that target specific groups.

The mortality rates in registries of patients with STEMI are highly affected by inclusion criteria and population characteristics.

BACKGROUND: Different mortality rates are reported in registries of patients with ST-segment elevation myocardial infarction (STEMI), but comparisons between registries are challenging. AIMS: To determine whether the higher mortality rate in our regional French registry (SCALIM) is related to different inclusion criteria and demographic characteristics. METHODS: The SCALIM registry included all patients with STEMI within the first 24 h in the region of Limousin, France (06/2011-01/2015). To compare mortality rates with other contemporary registries in France and European neighbouring countries, the others' inclusion criteria were applied to the SCALIM registry. RESULTS: Among 1501 patients included, in-hospital and 1-month mortality were 8.2% and 8.8% respectively, significantly higher than many other registries. The use of inclusion criteria from EMUST (France), MINAP (UK) or LOMBARDIMA (Italy) markedly decreased the number of enrolled patients by 64%, 36%, and 21%, respectively. When those inclusion criteria were applied to the SCALIM registry, difference in in-hospital and 1-month mortality rates between other registries and ours remained significant. In the multivariate analysis, age, initial acute pulmonary oedema (Killip class ≥2), complication occurring before percutaneous coronary intervention, absence of transfer to an interventional cardiology centre for primary angioplasty and lack of reperfusion therapy within 12 h were associated with higher risk of 1-month mortality (all p < 0.05). Age (65 versus 63.3 years, p < 0.001) was higher and reperfusion rate (84.2 versus 74.7%, p < 0.001) was significantly lower in SCALIM than FAST-MI, the national French registry on STEMI patients. Interestingly, the 3% of patients included in SCALIM who would be excluded from FAST-MI registry had 91% mortality at one month. CONCLUSION: Higher mortality rate in our regional SCALIM registry is in part due to differences in inclusion criteria and demographic data. Consensus should be made to harmonise inclusion criteria in STEMI registries for the sake of comparability.

Impact of Pulmonary Hypertension on Outcome in Patients with Severe Aortic Stenosis and Preserved Left Ventricular Ejection Fraction.

AIMS: The prognostic impact of elevated pulmonary arterial pressure (PAP) remains controversial in aortic stenosis (AS) and few studies focused on patients with preserved left ventricular ejection fraction (LVEF). We aimed to investigate the impact of pulmonary hypertension (PH), invasively derived, on survival in severe AS with preserved LVEF. METHODS AND RESULTS: Between 2000 and 2010, 749 patients (74 ± 8 years, 57% males) with preserved LVEF and severe AS without other valvular heart disease underwent cardiac catheterization. PH was defined as mean PAP > 25 mmHg. The mean follow-up was 4.6 ± 3.0 years. Overall, 32% (n = 241) of patients had PH. Surgical aortic valve replacement (SAVR) was performed in 91% of patients with 4.5% of 30-day mortality rate, significantly higher in patients with PH than without PH (7.5 vs. 3.5%, p = 0.014). In logistic regression, PH was an independent predictor of increased 30-day mortality (odds-ratio = 2.2, p = 0.04). Overall long-term survival was significantly reduced in patients with PH as compared to those without (10-year: 52 ± 5 vs. 68 ± 3%, p < 0.0001). Likewise, focusing on patients with SAVR showed significant reduced survival in those with PH (10-year: 57 ± 5 vs. 72 ± 3%, p < 0.0001). In multivariate analysis, after adjustment for relevant cofactors, PH was an independent predictor of mortality (hazard ratio = 1.5, p = 0.009). Using quartiles of mean PAP, only patients with most elevated values (Q4: mean PAP: 27-67mmHg) had significantly reduced survival, as compared to other quartiles (all p < 0.0001). CONCLUSION: In patients with severe AS and preserved LVEF, PH is an independent predictor of 30-day and long-term mortality patients. Nevertheless, only severely elevated PAP seems associated with reduced survival.

Prognostic impact of global left ventricular hemodynamic afterload in severe aortic stenosis with preserved ejection fraction.

INTRODUCTION: Global left ventricular (LV) afterload as assessed by valvulo-arterial impedance (Zva), may be an independent predictor of mortality in patients with severe aortic stenosis (AS) and preserved LV ejection fraction (LVEF). However, its quantification using echocardiography may be subject to error measurement. We aimed to determine the prevalence and impact on long-term survival of high Zva, purposely measured by cardiac catheterization. METHODS AND RESULTS: 676 patients with preserved LVEF and severe AS without other valvular heart diseases underwent cardiac catheterization. Zva was derived from catheterization and calculated as follows: mean aortic gradient+systolic blood pressure/indexed LV stroke volume. Zva was considered high when >5mmHg/mL/m(2) based on previous studies. Overall, high Zva was found in 42% of all AS patients. Four-year survival and 8-year survival were significantly reduced in patients with high Zva (74±3% and 57±4%) as compared to those with low Zva (85±2% and 74±3%; p=0.002). After adjustment for all other risk factors, Zva was independently associated with reduced long-term survival (hazard ratio [HR]=1.47 95% CI: 1.04-2.09; p=0.029). Of interest, high Zva remained associated with reduced survival as compared to low Zva, in patients with normal LV stroke volume, but was no longer significant in low flow patients (p=0.98). CONCLUSION: High Zva, estimated invasively in our study, is frequent in patients with severe AS, and appears as a robust and independent predictor of survival. Zva should be used as an additional parameter for risk stratification of severe AS, more particularly in patients with normal flow.

Prognosis importance of low flow in aortic stenosis with preserved LVEF.

AIMS: Previous studies using echocardiography suggested that a low flow (LF) defined as an indexed stroke volume (SVi) <35 mL/m(2) may be an important determinant of outcome in patients with severe aortic stenosis (AS). We sought to assess the prognostic importance of stroke volume derived from invasive data. The aim of this study was to determine the impact of LF, purposely derived from cardiac catheterisation data, on outcome of patients with severe AS and preserved LVEF. METHODS: Between 2000 and 2010, 768 patients with preserved LVEF (>50%) and severe AS (valve area ≤1 cm(2)) without other valvular heart disease underwent cardiac catheterisation. The long-term overall mortality was assessed as the primary end-point. RESULTS: Mean age was 74±8 years, 58% were men, 46% had coronary artery disease and mean LVEF was 72±10%. Low SVi was found in 27% (n=210) of patients with AS. As compared with patients with normal SVi, those with low SVi were significantly older (p<0.0001) with higher rate of atrial fibrillation (p<0.0001). Additionally, they had lower LVEF (p=0.046), aortic valve area (p<0.0001), mean pressure gradient (p<0.0001), systemic arterial compliance (p<0.0001) and higher systemic vascular resistances (p<0.0001). Eight-year survival was significantly reduced in patients with low SVi as compared with those with normal SVi (51±5% vs 67±3%; p<0.0001). After adjustment for all other risk factors, reduced SVi was independently associated with long-term mortality (HR=1.45, 95% CI 1.1 to 2.1; p=0.048). CONCLUSIONS: In patients with severe AS and preserved LVEF, LF, as assessed using cardiac catheterisation is frequent, and is an independent predictor of mortality. Consequently, the measurement of SVi should be systematically included in the assessment of these patients.

Cardiac amyloidosis: updates in diagnosis and management.

Amyloidosis is a severe systemic disease. Cardiac involvement may occur in the three main types of amyloidosis (acquired monoclonal light-chain, hereditary transthyretin and senile amyloidosis) and has a major impact on prognosis. Imaging the heart to characterize and detect early cardiac involvement is one of the major aims in the assessment of this disease. Electrocardiography and transthoracic echocardiography are important diagnostic and prognostic tools in patients with cardiac involvement. Cardiac magnetic resonance imaging better characterizes myocardial involvement, functional abnormalities and amyloid deposition due to its high spatial resolution. Nuclear imaging has a role in the diagnosis of transthyretin amyloid cardiomyopathy. Cardiac biomarkers are now used for risk stratification and staging of patients with light-chain systemic amyloidosis. Different types of cardiac complications may occur, including diastolic followed by systolic heart failure, atrial and/or ventricular arrhythmias, conduction disturbances, embolic events and sometimes sudden death. Senile amyloid and hereditary transthyretin amyloid cardiomyopathy have better prognoses than light-chain amyloidosis. Cardiac treatment of heart failure is usually ineffective and is often poorly tolerated because of its hypotensive and bradycardiac effects. The three main types of amyloid disease, despite their similar cardiac appearance, have specific new aetiological treatments that may change the prognosis of this disease. Cardiologists should be aware of this disease to allow early treatment.

Left atrial size is an independent predictor of overall survival in patients with primary systemic amyloidosis.

BACKGROUND: Primary systemic amyloidosis is a severe plasma cell disorder characterized by the extracellular deposition of amyloid fibrils in different organs. Echocardiography is usually performed to assess cardiac involvement. We hypothesized that in patients with systemic amyloidosis, simple echocardiographic measurement of the left atrial (LA) diameter indexed to the body surface area might provide an important risk marker for this disease. METHODS: Between 1997 and 2011, 134 patients were diagnosed with primary systemic amyloidosis and had echocardiography within 28 days; we collected their baseline characteristics and biological and echocardiographic data retrospectively. LA enlargement was defined as recommended as M-mode LA diameter greater or equal to 23 mm/m(2). RESULTS: One hundred and eleven patients (83%) had echocardiographic LA dimension data available (mean age 63±11 years; 61% men; 31% previously diagnosed with systemic hypertension). Mean left ventricular ejection fraction (LVEF) and interventricular septum thickness (IVST) were 62±12% and 14±4 mm, respectively. Mean follow-up was 2.8±2.9 years (maximum 12 years). Patients with LA enlargement had a slightly lower LVEF (P=0.08) and a significantly greater IVST (P<0.0001). Overall, 5-year survival was 57±5%. However, 1-year and 5-year survival rates were markedly reduced in patients with LA enlargement versus those without LA enlargement (61±7% and 39±8% vs 83±5% and 72±7%, respectively; P=0.0007). On multivariable analysis, after adjusting for age, sex, LVEF, IVST, presence of hypertension and creatinine concentration, LA enlargement remained an independent predictor of overall mortality at 5 years (hazard ratio 2.47; 95% confidence interval 1.11-5.90; P=0.02). CONCLUSION: LA enlargement, a surrogate marker of diastolic dysfunction, is an independent predictor of long-term mortality and may therefore help to enhance risk stratification and management of patients presenting with amyloidosis.