Symptomatic HF Research Articles

Age-specific diastolic dysfunction improves prediction of symptomatic heart failure by Stage B heart failure.

AimsWe investigated whether addition of diastolic dysfunction (DD) and longitudinal strain (LS) to Stage B heart failure (SBHF) criteria (structural or systolic abnormality) improves prediction of symptomatic HF in participants of the SCReening Evaluation of the Evolution of New Heart Failure study, a self‐selected population at increased cardiovascular disease risk recruited from members of a health insurance fund in Melbourne and Shepparton, Australia. Both American Society of Echocardiography and European Association of Cardiovascular Imaging (ASE/EACVI) criteria and age‐specific Atherosclerosis Risk in Communities (ARIC) study criteria, for SBHF and DD, and ARIC criteria for abnormal LS, were examined.Methods and resultsInclusion criteria were age ≥60 years with one or more of self‐reported ischaemic or other heart disease, irregular or rapid heart rhythm, cerebrovascular disease, renal impairment, or treatment for hypertension or diabetes for ≥2 years. Exclusion criteria were known HF, or ejection fraction <50% or >mild valve abnormality detected on previous echocardiography or other imaging. Echocardiography was performed in 3190 participants who were followed for a median of 3.9 (interquartile range: 3.4, 4.5) years after echocardiography. Symptomatic HF was diagnosed in 139 participants at a median of 3.1 (interquartile range: 2.1, 3.9) years after echocardiography. ARIC structural, systolic, and diastolic abnormalities predicted HF in univariate and multivariable proportional hazards analyses, whereas ASE/EACVI structural and systolic, but not diastolic, abnormalities predicted HF. ARIC and ASE/EACVI SBHF criteria predicted HF with sensitivities of 81% and 55%, specificities of 39% and 76%, and C statistics of 0.60 (95% confidence interval: 0.57, 0.64) and 0.66 (0.61, 0.71), respectively. Adding ARIC DD to SBHF increased sensitivity to 94% with specificity of 24% and C statistic of 0.59 (0.57, 0.61), whereas addition of ASE/EACVI DD to SBHF increased sensitivity to 97% but reduced specificity to 9% and the C statistic to 0.52 (0.50, 0.54, P < 0.0001). Addition of LS to ARIC or ASE/EACVI SBHF criteria had minimal impact on prediction of HF.ConclusionsAge‐specific ARIC DD criteria, but not ASE/EACVI DD criteria, predicted symptomatic HF, and addition of age‐specific ARIC DD criteria to ARIC SBHF criteria improved prediction of symptomatic HF in asymptomatic individuals with cardiovascular disease risk factors. Addition of LS to ASE/EACVI or ARIC SBHF criteria did not improve prediction of symptomatic HF.

Sex Differences in Outcomes and Responses to Spironolactone in Heart Failure With Preserved Ejection Fraction: A Secondary Analysis of TOPCAT Trial

ObjectivesThis study sought to investigate sex differences in outcomes and responses to spironolactone in patients with heart failure with preserved ejection fraction (HFpEF). BackgroundHFpEF affects women more frequently than men. Sex differences in responses to effects of mineralocorticoid antagonists have not been reported. MethodsThis was an exploratory, post hoc, non-pre-specified analysis of the TOPCAT (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function) trial. Subjects with symptomatic HF and a left ventricular ejection fraction ≥45% were randomized to spironolactone or placebo therapy. Subjects enrolled from the Americas were analyzed. The primary outcome was a composite of cardiovascular (CV) death, cardiac arrest, or HF hospitalization. Secondary outcomes included all-cause mortality, CV, and non-CV mortality and CV, HF, and non-CV hospitalization. Sex differences in outcomes and treatment effects were determined using time-to-event analysis. ResultsIn total, 882 of 1,767 subjects (49.9%) were women. Women were older with fewer comorbidities but worse patient-reported outcomes. There were no sex differences in outcomes in the placebo arm or in response to spironolactone for the primary outcome or its components. Spironolactone therapy was associated with reduced all-cause mortality in women (hazard ratio: 0.66; p = 0.01) but not in men (pinteraction = 0.02). ConclusionsIn TOPCAT, women and men presented with different clinical profiles and similar clinical outcomes. The interaction between spironolactone and sex in TOPCAT overall and in the present analysis was nonsignificant for the primary outcome, but there was a reduction in all-cause mortality associated with spironolactone therapy in women, with a significant interaction between sex and treatment arm. Prospective evaluation is needed to determine whether spironolactone therapy may be effective for treatment of HFpEF in women. (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT]; NCT00094302)

Heart failure with preserved ejection fraction as an independent risk factor of mortality after cardiothoracic surgery

BackgroundThe prognostic role of heart failure with preserved ejection fraction (HFpEF) remains unclear. This study aimed to assess HFpEF prognostic value after cardiothoracic surgery, adjusting for European System for Cardiac Operative Risk (EuroSCORE II) criteria. MethodsPatients with left ventricular ejection fraction (LVEF) ≥ 50% undergoing cardiothoracic surgery between 2012 and 2016 were included. Patients with HFpEF were compared to control patients with LVEF ≥ 50%. HFpEF was defined following 2016 European Society of Cardiology guidelines: LVEF ≥ 50%, symptomatic HF with New York Heart Association (NYHA) class 2 or greater, elevated brain natriuretic peptide (BNP) and relevant echocardiographic findings (LV hypertrophy, LA enlargement, or diastolic filling anomaly). The primary endpoint was in-hospital mortality, and the secondary endpoint was postoperative shock. Multivariate analyses were performed to determine mortality and shock risk-factors. ResultsAmong 1743 patients, 427 (24.5%) presented HFpEF. HFpEF was highly associated with in-hospital mortality (hazard ratio = 1.86; 95% confidence interval [CI], 1.16-2.98; P = .01). This association remained independent when adjusting for EuroSCORE II (adjusted hazard ratio = 1.6; 95% CI, 1.0-2.6; P = .049). Postoperative shock occurred more in HFpEF than in control patients (17.8% vs 6.7%; P < .001). HFpEF was an independent risk factor of postoperative shock (adjusted odds ratio = 2.9; 95% CI, 1.5-3.0; P < .001). ConclusionsHFpEF was an independent risk-factor of mortality and postoperative shock after cardiothoracic surgery, after adjustment regarding EuroSCORE II.

Development of screening echocardiogram for detection of asymptomatic left ventricular dysfunction

Clinical data about heart failure make it clear that there is a need to develop a limited echocardiogram assisted by automated functions as a screening tool to identify people who have asymptomatic left ventricular dysfunction and who can potentially benefit from proven therapies to prevent the development of symptomatic HF. Our preliminary tests show that an abbreviated version of an echo consisting of only 6 views can provide enough information for the binary screening. Six expert echo readers achieved near-perfect performance in identifying normal vs. abnormal echoes using 6 views, as compared to the diagnosis based on the full echocardiogram. The ground truth about the geometry of the heart was provided by one expert echo reader in the form of drawings and measurements. The drawings were used as a prior in a computational model that extracts the contour of the left ventricle as the shortest path in a log-polar (complex log) representation of the ventricle. This model may represent the first step in the development of an automated function for screening echocardiogram.

Heart failure with preserved ejection fraction as risk factor of mortality after cardiothoracic surgery

While heart failure with preserved ejection fraction (HFpEF) is associated with poor medical outcomes, its prognostic role in cardiothoracic surgery is still unclear. Conversely, EuroSCORE II is the most proven and used risk stratification score in such setting. This study aimed to assess HFpEF prognostic value after cardiothoracic surgery, taking into account EuroSCORE II. In a prospective cohort, patients with LVEF ≥ 50% undergoing cardiothoracic surgery were included. HFpEF patients were compared to control patients. HFpEF was defined as per 2016 ESC guidelines: LVEF ≥ 50%, symptomatic HF with New York Heart Association (NYHA) ≥ 2 and elevated BNP. Primary endpoint was time to intrahospital mortality; secondary endpoint was postoperative shock. Multivariate survival and logistic regression analyses were performed. Among 1743 patients included. Four hundred and twenty-seven (24.5%) presented HFpEF. Mortality was higher among HFpEF patients as compared to control patients (7.0% vs 3.2%, P -value < 0.001). HFpEF was independently associated with postoperative intrahospital mortality (adjusted hazard-ratio = 1.6 [95 CI 1.0–2.6], P = 0.049). HFpEF patients presented with more postoperative shock than control patients (17.8% vs. 6.7% P < 0.001). HFpEF was independently associated with postoperative shock (adjusted odd-ratio = 2.9 [95CI 1.5–3.0], P < 0.001). For a given EuroSCORE II, patients presenting with HFpEF had increased postoperative mortality as compared with control patients. HFpEF is an independent risk factor regarding postoperative cardiothoracic surgery.

Novel method to assess intrinsic heart rate recovery in ambulatory ECG recordings tracks cardioprotective effects of chronic autonomic regulation therapy in patients enrolled in the ANTHEM-HF study.

BackgroundPostexercise heart rate recovery (HRR) is a powerful and independent predictor of mortality. Autonomic regulation therapy (ART) with chronic vagus nerve stimulation (VNS) has been shown to improve ventricular function in patients with chronic heart failure. However, the effect of ART on HRR in patients with heart failure remains unknown.MethodsA new measure involving quantification of intrinsic HRR was developed for 24‐hr ambulatory ECG (AECG) recordings based on spontaneous heart rate changes observed during daily activity in patients with symptomatic heart failure and reduced ejection fraction. Intrinsic HRR values were compared in 21 patients enrolled in the ANTHEM‐HF study (NCT01823887) before and after 12 months of chronic ART (10 Hz, 250 μs pulse width, 18% duty cycle, maximum tolerable current amplitude after 10 weeks of titration) and to values from normal subjects (PhysioNet database, n = 54).ResultsWith chronic ART, average intrinsic HRR was improved as indicated by a shortening of the rate‐recovery time constant by 8.9% (from 12.3 ± 0.1 at baseline to 11.2 ± 0.1 s, p < .0001) among patients receiving high‐intensity stimuli (≥2 mA). In addition, mean heart rate decreased by 8.5 bpm (from 75.9 ± 2.6 to 67.4 ± 2.9 bpm, p = .005) and left ventricular ejection fraction (LVEF) increased by 4.7% (from 32.6 ± 2.0% to 37.3 ± 1.9%, p < .005).ConclusionUsing a new technique adapted for 24‐hr AECG recordings, intrinsic HRR was found to be impaired in patients with symptomatic HF compared to normal subjects. Chronic ART significantly improved intrinsic HRR, indicating an improvement in autonomic function.

Abstract P2-11-06: HER2 positive breast cancer and subclinical cardiotoxicity by echocardiogram 2D Strain, Do chemotherapy sequence matter?

Abstract Background: Even when there are free schemes of anthracyclines, the biological subtype HER2+ can be exposed to cardiotoxic drugs anthracyclines (A) and/or trastuzumab(H). It has been demonstrated that the LVEF is not sensitive to detect early cardiac changes and could be within normal ranges but with irreversible cardiac dysfunction. 2D speckle tracking and cardiac biomarkers (TnI and NT-proBNP) have shown more sensitivity to define early myocardial damage. Adjuvant trial FinHER suggests lower cardiotoxicity (0.5%) when taxanes (T)+H are given before A. Our objectives were: 1)To show higher sensitivity of the longitudinal strain in the echo to detect cardiotoxicity compared to the LVEF 2)To describe if there are any differences in the cardiotoxicity in relation with the chemotherapy sequence used. Patients and methods: A retrospective cohort of patients diagnosed with breast cancer from February 2008 to January 2016 was obtained, in which 46 patients with HER2 positive breast cancer were included, most in the context of neoadjuvant or adjuvant chemotherapy treated with sequential chemotherapy (A→T+H vs T+H→A), with a cumulative dose of 240 mg/m2 of doxorubicin. A basal echo was done, as well at 3, 6, 9, 12 months after the beginning of the chemotherapy to determine LVEF and early cardiac damage parameters, such as longitudinal strain. Cardiotoxicity was determined with a symptomatic HF with a decline of LVEF &amp;gt;5% or LVEF ≤55% or asymptomatic HF with a decline ≥10% or in LVEF or LVEF ≤55%. A fall ≥15% was considered a significant decline of the longitudinal strain Results: 1 patient (2.1%)presented symptomatic HF (NYHA III). Asymptomatic cardiotoxicity was present in 9 patients (19.6%), 9 (19.6%), 11 (23.9%), and 13 (28.3%) at the 3, 6, 9, and 12 months respectively. The mean LVEF were (66±6.6), (63±9.0), (65±7.0), (65±6.4), and (63±6.9) at the basal, 3, 6, 9, and 12 months measurements respectively, with a non-significant “p” value. Significant decline in the longitudinal strain was observed in 10 patients (21.7%, p=0.012), in 13 patients (28.3%, p=0.034), in 15 patients (32.6%, p=0.95), and in 18 patients (39.1%, p=0.07), at the 3, 6, 9, and 12 months measurements respectively. When comparing the cardiotoxicity group vs the non cardiotoxicity groups no significant differences were observed with other risk factors as: HTN, dyslipidemia, carbohydrate intolerance, DM, radiotherapy, weight, cumulative doses of A, systolic-diastolic BP, glc levels, HDL, TG, and BMI. In the logistic regression analysis the longitudinal strain decline (≥15%) basal vs 3 months measurement had a OR 7.63 CI 95%(1.04-55.86) and the A→T + H sequence OR 7.7 CI 95%(1.076-55.43), were kept as independent variables for cardiotoxicity. Conclusions: As reported in literature the decline in the longitudinal strain was more sensitive than the LVEF to predict cardiotoxicity, thus this would allow to identify the highest risk individuals and to start a cardioprotective intervention. Due to the retrospective character of our study, we believe that in the neoadjuvant or adjuvant chemotherapy setting of sequential chemotherapy there is the need of prospective studies that evaluate the subclinical cardiotoxicity with more sensitive parameters to confirm our data. Citation Format: Pérez-Montessoro V, Poblano-Aguilar I, Galindo-Uribe J, Vásquez-Ortiz Z, Armengol-Alonso A. HER2 positive breast cancer and subclinical cardiotoxicity by echocardiogram 2D Strain, Do chemotherapy sequence matter? [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-11-06.

A new use for maximum deflection index: Detection of intraventricular dyssynchrony

AimCRT has been shown to be very beneficial for patients with reduced LVEF, symptomatic HF and increased QRS width. But many patients do not benefit from CRT. Maximum deflection index (MDI) is a quantitive measure of the rapidity of depolarization of the myocardium. In previous studies, high MDI was found to indicate epicardial origin of ventricular tachycardia. We aimed to detect the relationship between echocardiographic intraventricular dyssynchrony and MDI. MethodsWe included 144 patients with HF, QRS≥120ms, LBBB, NYHA II-IV, LVEF<35% and scheduled for CRT (90 male, 54 female; mean age 65.3±9.9years). Septal-lateral >60ms delay for the beginning of systolic velocity in TDI and septum-posterior >130ms delay in M-mode were accepted as intraventricular dyssynchrony. The MDI was calculated by dividing the time from onset of the QRS complex to the earliest point of maximum deflection in V5-V6 by the QRS duration. ResultsSeptal-lateral delay was associated with MDI and QRS width in bivariate analysis. In logistic regression analysis, MDI (beta=0,264, p=0.001) and QRS width (beta=0,177, p=0.028) were found to be independent parameters for predicting significant septal-lateral delay. MDI was also associated with significant septum-posterior delay in bivariate correlations and ROC curve (p<0.05 for all). In bivariate analysis MDI was associated with intraventricular dyssynchrony in both non-strict LBBB (r=0.261, p=0.010) and strict LBBB (r=0.305, p=0.035) groups. ConclusionMDI is closely associated with all echocardiographic intraventricular dyssynchrony parameters. We suggest that MDI may be used as a marker to detect patients with increased intraventricular dyssynchrony. It may be useful to integrate MDI to CRT patient selection procedure in order to minimize nonresponders.

Abstract 417: BET Bromodomain Inhibition Blunts Heart Failure Progression and Fibrosis in Genetic Cardiomyopathy

Pathologic gene network activation is a hallmark of DCM and HF. We have used a chemical genetic strategy to study the role of the bromodomain and extraterminal (BET) family of epigenetic reader proteins in the regulation of gene expression in DCM. Transgenic mice carrying a human DCM mutation in phospholamban (PLN R9C ) develop profound fibrosis and DCM that progresses to symptomatic HF and early death. Temporal RNA-seq and pathway analysis identified pro-fibrotic gene expression as a key early driver of DCM progression. PLN R9C and age-matched wild type (WT) mice were treated daily with the potent and specific BET inhibitor JQ1 or vehicle from 8-weeks-of-age (preDCM) to 20-weeks-of-age. Vehicle-treated PLN R9C mice developed DCM with severely reduced LV function and negative cardiac remodeling. JQ1-treated PLN R9C mice had substantially better fractional shortening (27% vs. 15%, p=7x10 -10 ) and less negative remodeling (LV end diastolic diameter 3.9mm vs. 4.5mm, p=1x10 -5 ; LV wall thickness 0.69mm vs. 0.62mm, p=6x10 -6 ) compared to PLN R9C vehicle-treated mice at 20-weeks (n=15). Myocardial fibrosis was also significantly reduced by JQ1 (5.8% PLN R9C -JQ1 vs. 18.4% PLN R9C -vehicle, p=3x10 -5 ; n=3). RNA-seq in preDCM mice treated with JQ1 for 2 weeks demonstrated a decrease in pathologic gene activation. JQ1-treated PLN R9C mice versus vehicle treated mice had reduced expression of natriuretic peptides ( Nppa -31%, Nppb -29%; p&lt;0.001), less myosin heavy chain and actin isoform switching (ratio Myh6 / Myh7 PLN R9C -JQ1=12.2; PLN R9C -vehicle=8.8; ratio Actc1 / Acta1 PLN R9C -JQ1=39.3; PLN R9C -vehicle=12.1; p&lt;0.001), and lower pro-inflammatory gene expression ( Tgfb2 -48%, Tgfb3 -41%, Ctgf -21%, Gdf15 -56%; p&lt;0.001). At 20-weeks-of-age, continued treatment with JQ1 resulted in sustained suppression of cytokine expression with 2-fold lower levels of Tgfb2 and Tgfb3 compared to vehicle-treated PLN R9C mice. These data suggest that early induction of pro-fibrotic signaling is a key driver of pathologic remodeling in PLN R9C DCM. This study also identifies epigenetic control of pathologic gene activation by BET bromodomain proteins as a critical mechanism for cardiomyopathy progression and supports BET inhibition as a possible novel therapeutic strategy for HF.

Left ventricular partitioning in systolic heart failure subjects: addressing a mechanistic void with current therapies.

ICD patients with narrow QRS, CRT non-responders, and functional MR patients all have one mechanistic failure mode that is left untreated - the scar left behind following an MI. ICDs, CRTs, and MitraClip implantation are all well-proven therapies, but the Parachute device may address the mechanistic void that remains after each of these therapies has been used and may further improve patients' outcomes. A pooled analysis of 134 subjects was conducted using the first three clinical trials which included subjects with symptomatic ischaemic HF with LV wall motion abnormalities secondary to MI, and an LV ejection fraction less than 40%. The two-year cumulative mortality rate was 12.9%, with 8.7% in the first year and an increment of 4.2% in the second, which is a 53% reduction as compared to the first year. There is a significant proportion of patients with ischaemic heart failure being excluded from cardiac rhythm management (CRT, etc.), leaving a large treatment gap until mechanical support devices (LVAD) or heart transplantation in progressive heart failure are indicated. Along with other heart failure devices, Parachute may be a useful treatment modality, addressing a mechanistic void in the treatment of this disease. Current data support improvements in haemodynamics, functional capacity, six-minute walk distance, quality of life and a promising decline in mortality two years after Parachute implantation.

Combining angiotensin II receptor 1 antagonism and neprilysin inhibition for the treatment of heart failure

ABSTRACTSacubitril/valsartan is a novel, first-in-class drug, which combines a neprilysin inhibitor with an angiotensin receptor blocker. Sacubitril inhibits neprilysin endopeptidase, blocking the catabolism of natriuretic peptides (NP), thereby increasing their bioavailability. Valsartan counterbalances the increase of angiotensin II that results from neprilysin inhibition, exerting also the beneficial effects of angiotensin receptor blockers seen in previous HF trials. PARADIGM-HF trial has proved the superiority of sacubitril/valsartan (LCZ696) over ACE inhibitor enalapril to reduce mortality and morbidity of symptomatic HF patients with reduced ejection fraction (HFrEF), setting the grounds for the replacement of ACE inhibitors by sacubitril/valsartan in the management of HFrEF. Sacubitril/valsartan is currently being tested in a phase III trial (PARAGON-HF) in patients with HF with preserved EF. PARAGON-HF is also expected to provide further data regarding the long-term safety of sacubitril/valsartan, hopefully to alleviate concerns regarding the effects of neprilysin inhibition on cognitive function.

Burdensome Physical and Depressive Symptoms Predict Heart Failure–Specific Health Status Over One Year

ContextHeart failure (HF)-specific health status (symptom burden, functional status, and health-related quality of life) is an important patient-reported outcome that is associated with palliative care needs, hospitalizations, and death. ObjectivesTo identify potentially modifiable patient-reported factors that predict HF-specific health status over one year. MethodsThis was a prospective cohort study using data from the Patient-Centered Disease Management trial. Participants were identified using population-based sampling of all patients with an HF diagnosis at four VA Medical Centers. Patients were enrolled with reduced HF-specific health status (i.e., significant HF symptoms, limited functional status, and poor quality of life, defined by a Kansas City Cardiomyopathy Questionnaire [KCCQ] score <60). Patient-reported factors at baseline were chest pain, other noncardiac pain, dry mouth, numbness/tingling, constipation, nausea, cough, dizziness, depressive symptoms (Patient Health Questionnaire–9), and spiritual well-being (validated, single-item measure). Patients reported HF-specific health status (KCCQ) at 3, 6, and 12 months. ResultsOf 384 U.S. veterans, 42% screened positive for depression and 76% described burdensome physical symptoms at baseline. In bivariate analyses, all patient-reported factors were correlated with KCCQ score over one year. Multivariable mixed-effect modeling showed that baseline chest pain, numbness/tingling, depressive symptoms, and higher comorbidity count predicted HF-specific health status over the following year. ConclusionBurdensome physical and depressive symptoms independently predicted subsequent HF-specific health status in patients with symptomatic HF. Whether addressing these aspects of the patient experience can improve health status and well-being in symptomatic HF should be studied further.

The prognostic impact of diastolic dysfunction in patients with chronic heart failure and post-acute myocardial infarction: Can age-stratified E/A ratio alone predict survival?

ObjectiveTo determine the prognostic implications of diastolic filling grades and identify whether age-stratified E/A ratio alone can identify patients at high risk of death post-AMI and HF. We hypothesized that in response to ageing and pathology, a normal E/A (>1) could be considered abnormal in patients post-AMI older than 65years, and that in patients with symptomatic HF, a normal E/A always represents advanced diastolic dysfunction. Methods and resultsThis is a sub-analysis of the Meta-analysis Research Group in Echocardiography (MeRGE) which combined individual patient data from 30 prospective studies and demonstrated that restrictive filling was an important and independent predictor of all-cause mortality. This sub-analysis is restricted to those studies in which continuous E/A data were available (20 studies) and includes a total of 3082 AMI and 2321 HF patients. Patients were classified at the time of echocardiography into four filling patterns: normal, abnormal relaxation, pseudonormal, and restrictive filling. Post-AMI patients were divided into four groups on the basis of age and E/A, while patients with HF were classified into three groups, based on only E/A. Mortality across groups was compared using Kaplan–Meier survival analysis and Cox proportional hazards. In multivariable analyses in the AMI patients, age-stratified E/A was an independent predictor of outcome (HR 1.43 (95% CI: 1.31–1.56)), and in the HF cohort, E/A was confirmed as an independent predictor of mortality (HR 1.12 (95% CI 1.09–1.16)) alongside age and ejection fraction. ConclusionsAge-stratified E/A is an independent predictor of mortality after AMI and in HF patients, regardless of left ventricular ejection fraction, age and gender. E/A ratio could be a first step echocardiographic risk stratification, which could precede and indicate the need for more advanced diagnostic and prognostic considerations in high-risk AMI and HF patients.

Outcomes in World Health Organization Group II Pulmonary Hypertension: Mortality and Readmission Trends With Systolic and Preserved Ejection Fraction–Induced Pulmonary Hypertension

BackgroundHeart failure with preserved ejection fraction (HFpEF) has been increasingly recognized as a leading cause of pulmonary hypertension (HFpEF-PH). It remains unknown how HFpEF-PH fares in relation to systolic HF (reduced ejection fraction)–induced PH (HFrEF-PH). Therefore, we sought to determine the long-term morbidity and mortality of HFpEF-PH and HFrEF-PH. Methods and ResultsWe studied all patients over a 6-year period with symptomatic HF and severe PH (PASP ≥65 mm Hg) in The Bronx, New York. We classified patients as having either preserved (≥50%) or reduced (≤35%) left ventricular ejection fraction. Trends in mortality and HF readmission rates were defined in 650 patients (HFrEF-PH: n = 277; HFpEF-PH: n = 373). HFpEF-PH patients were older and more often female and white. HFrEF-PH patients were more often black, had ischemic cardiomyopathy, and were on typical HF drug regimens. Patients with HFpEF-PH had a significantly increased all-cause 5-year mortality (52% vs 42%; P = .024). HFpEF-PH was a significant predictor of mortality (adjusted hazard ratio 1.70; P = .012). Patients with HFrEF-PH had more HF readmissions (≥1) than patients with HFpEF-PH (28.6% vs 15%; P = .003), especially within the 1st year (9.1% vs 1.7%; P = .005). ConclusionsPatients with HFrEF-PH and HFpEF-PH have a significantly elevated long-term mortality, with HFpEF-PH having a higher 5-year mortality rate. These findings testify to the overall poor prognosis of World Health Organization Group II PH, especially HFpEF-PH.

Advanced Practice Registered Nurses (APRN): Educating Present and Future Leaders in Palliative Care (S744)

patient-reported factors (i.e., depression, spiritual well-being, symptoms) were used to determine which factors were independently associated with each outcome. Results. The study included 384 Veterans (mean age 68 years, 97% male, 82% white) with a mean KCCQ score of 38, indicating reduced health status. Demographics and clinical covariates were not significantly associated with the outcomes. Depression, spiritual well-being and several nonHF-specific symptoms were independently associated with HF-specific QOL (p<0.0001) and health status (p<0.0001). Only depression and spiritual well-being were associated with overall QOL (p<0.0001). Variability due to patient-reported factors (i.e., depression, spiritual well-being, chest pain, numbness, dizziness) was 32% for HF-specific QOL, 29% for HF-specific health status and 23% for overall QOL. Conclusions. Depression, spiritual well-being and several non-traditional HF-related symptoms are modifiable patient-reported factors that were independently associated with HF-specific QOL and health status in symptomatic HF patients. Implications for research, policy, or practice. A comprehensive palliative care approach that targets patient-reported factors may influence HF-specific QOL and health status.

Are the guidelines universal and time-independent?

I was much interested in reading the exhaustive paper by Andrew S Coats and Louise G. Shewan on the process of preparation of the Guidelines released by the European Society of Cardiology (ESC), compared to those of other guideline bodies, and the “Inconsistences in the development of the ESC Clinical Practice Guidelines for Heart Failure”. I would like to raise few further issues on both consistency and applicability of the modern guidelines. Firstly, to whom are the guidelines targeted? And who are the expected users? This is relevant both to the preparation of the documents and the formulation of the recommendations. It has been reported that the current international guidelines, taken as a whole, could not be applied inmost low-income countries; approximately3⁄4 of the world population would therefore not belong to the group of intended users of most modern guidelines. Furthermore, when we are discussing on adherence to the guideline recommendations what guidelines are we talking about? A recent survey made by the ESC among the countries associated to the Society showed that only in half of them the ESC guidelines were formally acknowledged as reference for the clinical practice, the others had their own cardiology guidelines or did not have published cardiology guidelines at all. This may generate somemisunderstanding on the application of the concept of adherence to the recommendations. Instead it seems clearwhom theUS guidelines are addressing: just the US patient populations (and clinicians) [1]. A relevant example dealswith Ivabradine, whose indication criteria are discussed in the Coats and Shewan editorial. This drug has been tested in chronic HF patients in the SHIFT trial [2], that enrolled 6558 patients in 37 countries (not in the US). The results were positive, the drug was approved by the regulatory EMA and has been included in the ESC guidelineswith a IIa recommendation. However it was not even mentioned in the 2013 version of ACC/AHA HF guidelines. For patients and physicians residing out of North America this approach can create important disadvantages by omitting a possibly helpful option for the care of symptomatic chronic HF patients. Secondly, in general, in the guidelines thedrugs are recommended at “target doses” employed in the trials onwhich their putative efficacy and regulatory approval are based, and are considered “optimal medical therapy” [3]. Information about effectiveness of other doses, lower or higher, seldom is available. However, in contemporary registries in chronic HF, for which therapy is particularly complex, large segments of the affected population fail to receive the recommended drugs and substantially less than half receive guidelines-based “target doses”. This was apparent from the 12country 2010 European HF Survey of the ESC [4]. These results are confirmed in the CIBIS-ELD trial, in which bisoprolol and carvedilol (beta blockers commonly used in clinical practice) were randomized in elderly patients with chronic HF and then force-titrated to ESC guidelines targets. At least 50% of the target dose was achieved in only 55% of the patients [5]. Similar results were also obtained in community studies [6,7]. In fact the target doses recommended in the current guidelines of most recommended treatments are those predefined as targets in remote studies, and systematically confirmed in guidelines as “optimal medical therapy” in spite of evidence of increasingly diverging clinical practice. This is an issue to be solved. If the recommended target doses are appropriate, we might infer that most patients currently are treated inadequately. Alternatively, we should seriously wonder whether the range of doses currently used in clinical practice actually represents patient needs and drug tolerability in the current era.

Entendendo a disfunção diastólica assintomática na prática clínica

1 . Cardiac dysfunction, either systolic or asymptomatic diastolic, has a high prevalence in the adult population older than 45 years, and is a phase during which the patient can progress to the clinical form of HF; this transition brings a five-fold increase in mortality 2 . Identifying patients with asymptomatic cardiac dysfunction may allow the implementation of nonpharmacological or pharmacological interventions aiming at reversing heart functional and structural abnormalities, thus delaying the onset of symptomatic HF. The concept that HF has progressive stages and is therefore a preventable condition was proposed by the American College of Cardiology (ACC) and the American Heart Association (AHA) 3 and was incorporated by the Chronic HF Guidelines of the Brazilian Society of Cardiology 4 . HF with normal ejection fraction (HFNEF) is now a new epidemic that affects elderly hypertensive patients and represents more than 50% of patients hospitalized for HF. The onset of HFNEF is preceded by diastolic abnormalities such as slowing in relaxation and alterations in the filling pressures and structure of the left ventricle (LV) - left ventricular hypertrophy (LVH), and increased left atrial volume (LAV). Thus, it is important to detect these abnormalities in a preclinical phase 2 . Asymptomatic systolic dysfunction is easily recognized by clinicians using a cardiac imaging method, for the presence of left ventricular ejection fraction (LVEF) < 50%. The characterization of asymptomatic diastolic dysfunction (DD) is made by a triad consisting of absence of HF symptoms, evidence of DD and LVEF ≥ 50%, and its presence is a marker for the onset of symptomatic HF and reduced life expectancy 5 .

Abstract 19519: Patient Health Questionnaire-9 Correlates with Kansas City Cardiomyopathy Questionnaire and Minnesota Living with Heart Failure Questionnaire in Measuring Heart Failure Patient Well-Being and Predicting Outcomes

Introduction: The assessment of patient well-being and correlation with outcomes is especially difficult, particularly with HF patients. Currently, the time-consuming Kansas City Cardiomyopathy Questionnaire (KCCQ) and Minnesota Living with Heart Failure Questionnaire (MLHFQ) are typically used only in research protocols; conversely, the PHQ-9 is a much simpler questionnaire that can be completed and scored in a typical clinical setting. Hypothesis: We hypothesized that the scores of the PHQ-9 correlate with the scores of the KCCQ and MLHFQ, and that for clinical purposes, it may be beneficial to substitute the longer questionnaires with the PHQ-9. Methods: Using data obtained through the Vanderbilt Main Heart Registry, we compared patient scores on the KCCQ and MLHFQ in each depression category (none, mild, moderate, moderately-severe, and severe) in 294 patients with heart failure, as defined by patient PHQ-9 scores. We also assessed survival data for the patients that have been followed up to two years with annual PHQ-9 scores to evaluate the correlation between depression category and mortality. Results: The study group (N=294) was 55 years (range 18-90) and 60% male, most with symptomatic HF (93% ≥ NYHA II)( Table 1.). Twenty-five percent of patients with severe depression are deceased. Preliminary results indicate there is a direct correlation between PHQ-9 category and corresponding KCCQ (p &lt; 0.001) and MLHFQ (p &lt; 0.001) scores (Figure 1.). Conclusion: Our findings suggest that the PHQ-9 can be readily used as a screen for depression and quality of life in HF patient in the clinical setting. Additionally, PHQ-9 score appears highly correlated to major outcomes.

Effectiveness of Implantable Cardioverter Defibrillators and Cardiac Resynchronization Therapy in Heart Failure

Randomized trials and observational data have consistently demonstrated the benefit of ICDs for primary prevention of SCD in patients with HF and LVSD or secondary prevention in patients with a history of prior ventricular arrhythmias or aborted SCD, most of whom have HF. Secondary and post hoc analyses of trial data, as well as observational data, generally suggest that ICD therapy is effective in most selected subpopulations, such as the elderly and patients with NYHA class IV HF symptoms, but some studies suggest that ICDs may not be as effective in women and those with severe comorbidities, such as ESRD. Although there is limited evidence for an incremental benefit achieved with dual-chamber compared with single-chamber ICDs, the former devices are placed almost twice as frequently in the United States. Finally, observational data have recently shown that ICD procedural outcomes are improved when the device is placed by an electrophysiologist and at a high-volume hospital. More recently, clinical trials have demonstrated that cardiac resynchronization therapy improves quality of life and lowers rates of HF hospitalization in patients with symptomatic HF, LVSD, and a prolonged QRS complex already receiving optimal medical management; recent trial results have also suggested a mortality benefit with CRT in this population. In addition, recent trial data suggest that CRT reduces nonfatal events among mildly symptomatic patients (NYHA class I-II); however, the cost-effectiveness of CRT in this population remains unclear. As with ICDs, secondary and post hoc analyses of trial data as well as observational data suggest that CRT remains effective in most selected subpopulations, including stable NYHA class IV patients, the very elderly, and women. Recent observational work has suggested that CRT may not benefit patients with an RBBB QRS morphology to the same extent as those with an LBBB pattern, although because more conclusive studies are currently lacking, the guidelines do not tailor the recommendations based on QRS morphology. In summary, ICDs, CRT-P, and CRT-D represent important and effective treatment modalities for select patients with HF. Additional investigation is required to better determine which patient populations most benefit from these cardiac devices and which device, implanting physician, and hospital characteristics optimize outcomes with these cardiac devices.

1397P - Cardiac Safety of (NEO) Adjuvant Trastuzumab in the Brazilian Community Setting: A Single Center Experience

ABSTRACT Background Trastuzumab-associated cardiotoxicity (TAC) has been established in the context of clinical trials. However, when newly registered agents are used in a broader patient population, their safety profile does not always mirror that of the pivotal trials. Trastuzumab (T) only became available in the Brazilian public sector in 2008 and herein we report our off-trial experience so far. Methods Retrospective, single center cohort of HER-2 positive breast cancer patients (pts) treated with (neo)adjuvant chemotherapy and T from July 2008 to March 2012. 95.3% were treated according to local protocol (11.4% TCH; 83.9% AC-TH). Major cardiac event (MCE) was defined as a left ventricular ejection fraction (LVEF) drop of 10% and absolute drop to Results 237 women were identified: median age 53 y (27-83), 99.6% ECOG-PS 0-1, median body mass index 27.4 kg/m2 (17 – 46), 30.4% had hypertension (HTN), 8.8% had diabetes mellitus (DM), 5.9% had previous cardiopathy. 54.8% had ER-positive tumors; 40.7% received neoadjuvant T; most were stage II or III (22.3% and 37.1%). Median number of ECHO assessments was 2.7 (0-6); 136 pts (57.2%) completed T as planned. 20.2% had MCE (13.9% discontinued T). 3.8% discontinued T due to symptomatic HF and 5% for non-cardiac reasons. 41.6% of MCE pts recovered cardiac function. Median initial LVEF was 64.83 ± 1.5 % (no event) vs 64.81 ± 1.5 % (MCE) p = 0.26; median 3-month LFVE was 64.67 ± 4 % (no event) vs 56.12 ± 3 % (MCE) p = 0.0036. HTN, DM, obesity, age, radiotherapy, use of anthracycline and previous cardiopathy were not significantly associated with TAC. Conclusions Our results suggest that TAC in our routine practice is slightly higher than reported in literature (6 to 17%), possibly reflecting selection bias in clinical trials. Symptomatic TAC was as expected for AC-TH (4%). We failed to identify risk factors for TAC, possibly due to the low number of events. Cardiac function must be closely monitored during T treatment and careful pt selection is crucial. Disclosure All authors have declared no conflicts of interest.