Diagnostic and Clinical Value of FFRCT in Stable Chest Pain Patients With Extensive Coronary Calcification: The FACC Study.

BACKGROUND: The influence of extensive coronary calcifications on the diagnostic and prognostic value of coronary computed tomography angiography-derived fractional flow reserve (FFRCT) has been scantily investigated. OBJECTIVES: The purpose of this study was to investigate the diagnostic and short-term role of FFRCT in chest pain patients with Agatston score (AS) >399. METHODS: This was a prospective multicenter study of 260 stable patients with suspected coronary artery disease (CAD) and AS >399. FFRCT was measured blinded by an independent core laboratory. All patients underwent invasive coronary angiography (ICA) and FFR if indicated. The agreement of FFRCT ≤0.80 with hemodynamically significant CAD on ICA/FFR (≥50% left main or ≥70% epicardial artery stenosis and/or FFR ≤0.80) was assessed. Patients undergoing FFR had colocation FFRCT measured, and the lowest per-patient FFRCT was registered in all patients. The association among per-patient FFRCT, coronary revascularization, and major clinical events (all-cause mortality, myocardial infarction, or unstable angina hospitalization) at 90-day follow-up was evaluated. RESULTS: Median age and AS were 68.5 years (IQR: 63-74 years) and 895 (IQR: 587-1,513), respectively. FFRCT was ≤0.80 in 204 patients (78%). Colocation FFRCT (n = 112) showed diagnostic accuracy, sensitivity, and specificity to identify hemodynamically significant CAD of 71%, 87%, and 54%. The area under the receiver-operating characteristics curve (AUC) was 0.75. When using the lowest FFRCT (n = 260), per-patient accuracy, sensitivity, and specificity were 57%, 95%, and 32%, respectively. The AUC was 0.84. A total of 85 patients underwent revascularization, and FFRCT was ≤0.80 in 96% of these. During follow-up, major clinical events occurred in 3 patients (1.2%), all with FFRCT ≤0.80. CONCLUSIONS: Most patients with AS >399 had FFRCT ≤0.80. Using ICA/FFR as the reference revealed a moderate diagnostic accuracy of colocation FFRCT. Compared with the lowest per-patient FFRCT, colocation FFRCT measurement improved diagnostic accuracy and specificity. The 90-day follow-up was favorable with few coronary revascularizations and no major clinical events occurring in patients with FFRCT >0.80. (Use of FFR-CT in Stable Intermediate Chest Pain Patients With Severe Coronary Calcium Score [FACC]; NCT03548753).

Renal dysfunction, restrictive left ventricular filling pattern and mortality risk in patients admitted with heart failure: a 7-year follow-up study.

BACKGROUND: Renal dysfunction is associated with a variety of cardiac alterations including left ventricular (LV) hypertrophy, LV dilation, and reduction in systolic and diastolic function. It is common and associated with an increased mortality risk in heart failure (HF) patients. This study was designed to evaluate whether severe diastolic dysfunction contribute to the increased mortality risk observed in HF patients with renal dysfunction. METHODS: Using Cox Proportional Hazard Models on data (N = 669) from the EchoCardiography and Heart Outcome Study (ECHOS) study we evaluated whether estimated glomerular filtration rate (eGFR) was associated with mortality risk before and after adjustment for severe diastolic dysfunction. Severe diastolic dysfunction was defined by a restrictive left ventricular filling pattern (RF) (=deceleration time < 140 ms) by Doppler echocardiography. RESULTS: Median eGFR was 58 ml/min/1.73 m², left ventricular ejection fraction was 33% and RF was observed in 48%. During the 7 year follow up period 432 patients died. Multivariable adjusted eGFR was associated with similar mortality risk before (Hazard Ratio(HR)(eGFR 10 ml increase): 0.94 (95% CI: 0.89-0.99, P = 0.024) and after (HR(eGFR 10 ml increase): 0.93 (0.89-0.99), P = 0.012) adjustment for RF (HR: 1.57 (1.28-1.93), P < 0.001). CONCLUSIONS: In patients admitted with HF RF does not contribute to the increased mortality risk observed in patients with a decreased eGFR. Factors other than severe diastolic dysfunction may explain the association between renal function and mortality risk in HF patients.

The prognostic importance of a history of hypertension in patients with symptomatic heart failure is substantially worsened by a short mitral inflow deceleration time.

BACKGROUND: Hypertension is a common comorbidity in patients with heart failure and may contribute to development and course of disease, but the importance of a history of hypertension in patients with prevalent heart failure remains uncertain. METHODS: 3078 consecutively hospitalized heart failure patients (NYHA classes II-IV) were screened for the EchoCardiography and Heart Outcome Study (ECHOS). The left ventricular ejection fraction (LVEF) was estimated by 2 dimensional transthoracic echocardiography in all patients and a subgroup of 878 patients had additional data on pulsed wave Doppler assessment of transmitral flow available. A restrictive filling (RF) was defined as a mitral inflow deceleration time ≤140 ms. Patients were followed for a median of 6.8 (Inter Quartile Range 6.6-7.0) years and multivariable Cox regression models were used to assess the risk of all-cause mortality associated with hypertension. RESULTS: The study population had a mean age of 73 ± 11 years. 39% were female, 27% had a history of hypertension and 48% had a RF. Over the study period, 64% of the population died. Hypertension was not associated with increased risk of mortality, hazard ratio (HR) 0.95 (0.85-1.05). LVEF did not modify this relationship (p for interaction = 0.7), but RF pattern substantially influenced the outcomes associated with hypertension (p for interaction < 0.001); HR 0.75 (0.57-0.99) and 1.41 (1.08-1.84) in patients without and with RF, respectively. CONCLUSIONS: In patients with symptomatic heart failure, a history of hypertension is associated with a substantially increased relative risk of mortality among patients with a restrictive transmitral filling pattern.

The prognostic importance of lung function in patients admitted with heart failure.

AIMS: The purpose of the present study was to determine the prognostic importance for all-cause mortality of lung function variables obtained by spirometry in an unselected group of patients admitted with heart failure (HF). METHODS AND RESULTS: This was a prospective prognostic study performed as part of the EchoCardiography and Heart Outcome Study (ECHOS). This analysis included 532 patients admitted with a clinical diagnosis of HF. All patients underwent spirometry and echocardiography and the diagnosis of HF was made according to established criteria. Mean forced expiratory volume in 1 s (FEV(1)) was 65% of the predicted value [95% confidence interval (CI) 63-67%], mean forced vital capacity (FVC) was 71% of predicted (95% CI 69-72%), and FEV(1)/FVC was 0.72 (95% CI 0.71-0.73). FEV(1), FVC, and FEV(1)/FVC were all significant prognostic factors for all-cause mortality in univariate analyses. In a multivariate analysis, FEV(1) had independent prognostic value (hazard ratio 0.86 per 10% change, P < 0.001) after adjusting for demographic variables, known risk factors, ejection fraction, and self-reported chronic obstructive pulmonary disease. CONCLUSION: Pulmonary function provides significant prognostic information for all-cause mortality in patients admitted with HF. Spirometry therefore seems to be worth considering for all patients admitted with HF in order to identify patients at high risk.

Prognostic importance of a restrictive transmitral filling pattern in patients with symptomatic congestive heart failure and atrial fibrillation.

BACKGROUND: Restrictive diastolic filling pattern is associated with increased mortality in patients with myocardial infarction and heart failure. Most studies have excluded patients with atrial fibrillation. The aim of the present study was to assess the prognostic value of a restrictive filling pattern in patients with atrial fibrillation. METHODS: Doppler echocardiography including pulsed wave Doppler assessment of transmitral flow was performed in 880 patients with a clinical diagnosis of heart failure on hospital admission. Filling was considered restrictive when the mitral deceleration time

Predictors of right ventricular function as measured by tricuspid annular plane systolic excursion in heart failure.

INTRODUCTION: Tricuspid Annular Plane Systolic Excursion (TAPSE) has independent prognostic value in heart failure patients but may be influenced by left ventricular (LV) ejection fraction. The present study assessed the association of TAPSE and clinical factors, global and regional LV function in 634 patients admitted for symptomatic heart failure. METHODS & RESULTS: TAPSE were correlated with global and regional measures of longitudinal LV function, segmental wall motion scores and measures of diastolic LV function as measured from transthoracic echocardiography.LV ejection fraction, wall motion index scores, atrio-ventricular annular plane systolic excursion of the mitral annulus were significantly related to TAPSE. Septal and posterior mitral annular plane systolic excursion (beta = 0.56, p < 0.0001 and beta = 0.35, p = 0.0002 per mm, respectively) and non-ischemic etiology of heart failure (beta = 1.3, p = 0.002) were independent predictors of TAPSE, R(2) = 0.28, p < 0.0001. The prognostic importance of TAPSE was not dependent of heart failure etiology or any of the other clinical factors analyzed, P(interaction) = NS. CONCLUSION: TAPSE is reduced with left ventricular dysfunction in heart failure patients, in particular with reduced septal longitudinal motion. TAPSE is decreased in patients with heart failure of ischemic etiology. However, the absolute reduction in TAPSE is small and seems to be of minor importance in the clinical utilization of TAPSE whether applied as a measure of right ventricular systolic function or as a prognostic factor.

Prognostic importance of a short deceleration time in symptomatic congestive heart failure.

AIMS: A restrictive transmitral filling (RF) pattern predicts increased mortality in heart failure (HF) with reduced left ventricular (LV) systolic function. We performed a combined evaluation of LV function and RF for prognosis in patients with HF with and without systolic dysfunction. METHODS AND RESULTS: Doppler echocardiography was performed in 972 patients with symptomatic HF. RF was considered present when deceleration time (DT) was 140 ms. A DT >240 ms was defined as delayed relaxation. During a median of 51 months the unadjusted all-cause mortality rates were significantly increased among patients with RF vs. the non-RF group (1- and 4-year mortality was 25% and 54% vs. 17% and 43%). In a multivariable model, RF was a significant predictor of all-cause mortality (hazard ratio (HR)=2.0, 95% confidence interval (CI):1.5-2.6) whereas delayed relaxation was without prognostic importance (HR=0.9, CI:0.5-1.6). Repeating the multivariable model in subgroups of wall motion index (WMI) showed that RF was a strong predictor of mortality independent of WMI. For patients with LVEF of at least 50%, HR for RF was 2.0 (CI:1.1-3.4; p=0.02) and interaction between LVEF and RF was not significant. CONCLUSION: In a heterogeneous population hospitalised for symptomatic HF a restrictive transmitral filling pattern, defined as shortened deceleration time, during hospitalisation is an ominous prognostic sign independent of LV systolic function.

A randomised trial of a pre-synaptic stimulator of DA2-dopaminergic and alpha2-adrenergic receptors on morbidity and mortality in patients with heart failure.

BACKGROUND: By pre-synaptic stimulation of DA(2)-dopaminergic and alpha(2)-adrenergic receptors, nolomirole inhibits norepinephrine secretion from sympathetic nerve endings. We performed a clinical study with nolomirole in patients with heart failure (HF). METHODS: The study was designed as a multicentre, double blind, parallel group trial of 5 mg b.i.d. of nolomirole (n=501) versus placebo (n=499) in patients with severe left ventricular systolic dysfunction, recently in New York Heart Association (NYHA) class III/IV. The primary endpoint was time to all cause death or hospitalisation for HF, whichever came first. The study was event driven and required 420 primary events. The study was completed as scheduled. RESULTS: Mean age of patients was 70 years, and 73% were male. Heart rate and blood pressure were not different in the two treatment groups. There were no changes in blood pressure. There were 233 primary events in the nolomirole group versus 208 in the placebo group (p=0.1). There were 142/145 deaths and 369/374 all cause hospitalisations in the nolomirole/placebo groups. There were no differences in walking distance, quality of life or NYHA class. CONCLUSION: A dose of 5 mg b.i.d. of nolomirole was not beneficial (or harmful) in patients with heart failure.

Prognostic importance of pulmonary hypertension in patients with heart failure.

Pulmonary hypertension is a well-known complication in heart failure, but its prognostic importance is less well established. This study assessed the risk associated with pulmonary hypertension in patients with heart failure with preserved or reduced left ventricular (LV) ejection fractions. Patients with known or presumed heart failure (n = 388) underwent the echocardiographic assessment of pulmonary systolic pressure and LV ejection fraction. Patients were followed for up to 5.5 years. Increased pulmonary pressure was associated with increased short- and long-term mortality (p <0.0001 and p = 0.003, respectively). This relation was also present when stratifying patients by reduced or preserved LV function. A Cox proportional-hazards model apportioned a 9% increase in mortality per 5 mm Hg increase in right ventricular systolic pressure (p = 0.0008), independent of age and known chronic obstructive lung disease, heart failure, and impaired renal function. In conclusion, pulmonary hypertension is associated with increased short- and long-term mortality in patients with reduced LV ejection fractions and also in patients with preserved LV ejection fractions.

Right ventricular dysfunction as an independent predictor of short- and long-term mortality in patients with heart failure.

BACKGROUND: The prognostic importance of right ventricular (RV) dysfunction in heart failure (HF) has been suggested in patients with severe systolic heart failure. Tricuspid annular plane systolic excursion (TAPSE) is a simple echocardiographic measure of RV ejection fraction, but may be affected by co-existing chronic obstructive pulmonary disease (COPD). AIMS: To examine the prognostic information from TAPSE adjusted for the potential confounding effects of co-existing cardiovascular and COPD in a large series of patients admitted for new onset or worsening HF. METHODS AND RESULTS: Eight hundred and seventeen patients screened for participation in a large clinical trial by trans-thoracic echocardiography, including measurement of TAPSE, were followed for a median of 4.1 years (maximum 5.5 years). Decreased TAPSE as well as presence of COPD were independently associated with adverse short- and long-term survival, hazard ratio was 0.74 (p=0.004) for every doubling of TAPSE; and 2.4 (p<0.0001) for the presence of COPD. CONCLUSION: Decreased RV systolic function as estimated by TAPSE is associated with increased mortality in patients admitted for HF, and is independent of other risk factors in HF including left ventricular function. The co-existence of COPD is also associated with an adverse prognosis independent of the RV systolic function.

Effect of obesity and being overweight on long-term mortality in congestive heart failure: influence of left ventricular systolic function.

AIMS: Previous studies have suggested that a high body mass index (BMI) is associated with an improved outcome in congestive heart failure (CHF). However, the studies addressing this problem have not included enough patients with non-systolic heart failure to evaluate how left ventricular systolic function interacts with obesity on prognosis in CHF. The aim of this study was to evaluate how BMI influences mortality in patients hospitalized with CHF, and to address in particular whether the effect of BMI is influenced by left ventricular (LV) systolic function. METHODS AND RESULTS: Retrospective analysis of baseline and survival data for 4700 hospitalized CHF patients for whom BMI was available. LV systolic function, as assessed by wall motion index was available for 95% of the patients. Follow-up time ranged from 5 to 8 years. In the total population, the risk of death decreased steadily with increasing BMI from the underweight to the obese. Compared with normal weight, and adjusted for sex and age, risk ratios (RR) and 95% confidence limits were: underweight 1.56 (1.33-1.84), overweight 0.90 (0.83-0.97), obese 0.77 (0.70-0.86). Being underweight conferred a greater risk in CHF patients with normal systolic function [RR 1.66 (1.29-2.14), compared with normal weight] than in patients with reduced systolic function [RR 1.11 (0.87-1.42), P for interaction 0.03]. In patients with systolic dysfunction, obesity was associated with increased risk compared with normal weight [RR 1.21 (1.01-1.45)]. CONCLUSION: Increasing BMI in CHF is associated with a lower mortality, but the influence is complex and depends on left ventricular systolic function. Hence, in patients with systolic dysfunction obesity may indicate an increased risk.