Prognostic significance of medical therapy in patients with heart failure with reduced ejection fraction.

AIMS: The use of guideline-directed medical therapy (GDMT) among patients with heart failure (HF) with reduced ejection fraction (HFrEF) remains suboptimal. The SMYRNA study aims to identify the clinical factors for the non-use of GDMT and to determine the prognostic significance of GDMT in patients with HFrEF in a real-life setting. METHODS AND RESULTS: The SMYRNA study is a prospective, multicentre, and observational study that included outpatients with HFrEF. Patients were divided into three groups according to the status of GDMT at the time of enrolment: (i) patients receiving all classes of HF medications including renin-angiotensin system (RAS) inhibitors, beta-blockers, and mineralocorticoid receptor antagonists (MRAs); (ii) patients receiving any two classes of HF medications (RAS inhibitors and beta-blockers, or RAS inhibitors and MRAs, or beta-blockers and MRAs); and (iii) either patients receiving class of HF medications (only one therapy) or patients not receiving any class of HF medications. The primary outcome was a composite of hospitalization for HF or cardiovascular death. The study population consisted of 1062 patients with HFrEF, predominantly men (69.1%), with a median age of 68 (range: 20-96) years. RAS inhibitors, beta-blockers, and MRAs were prescribed in 76.0%, 89.4%, and 55.1% of the patients, respectively. The proportions of patients receiving target doses of guideline-directed medications were 24.4% for RAS inhibitors, 11.0% for beta-blockers, and 11.1% for MRAs. Overall, 491 patients (46.2%) were treated with triple therapy, 353 patients (33.2%) were treated with any two classes of HF medications, and 218 patients (20.6%) were receiving only one class of HF medication or not receiving any HF medication. Patient-related factors comprising older age, New York Heart Association functional class, rural living, presence of hypertension, and history of myocardial infarction were independently associated with the use or non-use of GDMT. During the median 24-month period, the primary composite endpoint occurred in 362 patients (34.1%), and 177 of 1062 (16.7%) patients died. Patients treated with two or three classes of HF medications had a decreased risk of hospitalization for HF or cardiovascular death compared with those patients receiving ≤1 class of HF medication [hazard ratio (HR): 0.65; 95% confidence interval (CI): 0.49-0.85; P = 0.002, and HR: 0.61; 95% CI: 0.47-0.79; P < 0.001, respectively]. CONCLUSIONS: The real-life SMYRNA study provided comprehensive data about the clinical factors associated with the non-use of GDMT and showed that suboptimal GDMT is associated with an increased risk of hospitalization for HF or cardiovascular death in patients with HFrEF.

Effect of Bendopnea on Achievement Medical Treatment Target Doses in Heart Failure.

BACKGROUND: The newly described bendopnea in heart failure (HF) is associated with increased cardiac filling pressures. The aim of the study was to show the effect of bendopnea follow-up on reaching optimal medical treatment doses in HF. METHODS: A total of 413 patients were screened, and we included 203 patients with HF who were previously evaluated for bendopnea. Demographic data, presence or absence of bendopnea, medical history, laboratory findings, and medical treatments were evaluated. Optimal medical therapy target doses at baseline and 3rd month were compared in groups with and without bendopnea. RESULTS: On admission, 64 patients (31.5%) had bendopnea. The rate of patients with bendopnea decreased in the 3rd month (n=42, 20.7%). The proportion of patients who used at least 50% of the recommended medical treatment dose on admission and in the 3rd month was compared; angiotensin-converting enzyme inhibitor /angiotensin receptor blockers use increased from 40.6% to 71.9% in those with bendopnea (P=0.013), from 56.1% to 81.3% in those without bendopnea (P<0.001) and beta-blockers use increased from 28.2% to 60.9% in those with bendopnea (P=0.042), from 31.6% to 69.8% in those without bendopnea (P<0.001). However, aldosterone antagonists use decreased from 70.3% to 67.2% in those with bendopnea (P=0.961), from 68.4 % to 64.1% in those without bendopnea (P=0.334). Bendopnea was independently effective in achieving ACE-I/ARB target doses (OR: 0.359, CI 95%: 0.151-0.854, P=0.020). CONCLUSION: Bendopnea follow-up in HF patients can provide a significant improvement in reaching the recommended treatment target doses.

Prognostic Significance of High-Sensitivity Troponin T in Nonischemic Heart Failure with Reduced Ejection Fraction.

OBJECTIVE: Cardiac biomarkers can help diagnose and predict heart failure prognosis. High-sensitivity troponin T has frequently been investigated in ischemic heart failure studies. However, the relation between high-sensitivity troponin T and mortality in nonischemic heart failure and its level indicating poor prognosis remain unclear. This study aimed to show whether high-sensitivity troponin T is a predictor of all-cause mortality and the cut-off value for high-sensitivity troponin T in patients with nonischemic heart failure with reduced ejection fraction. METHODS: We included 249 nonischemic heart failure patients with left ventricular ejection fraction ≤ 40%, age ≥ 18 years, and high-sensitivity troponin T level known. RESULTS: Of the patients, 59.8% were male, 73.5% were New York Heart Association I or II, and the median age was 64. High-sensitivity troponin T value of the patients was 18 ng/L [inter-quartile range, 10-34]. The cut-off value of high-sensitivity troponin T for all-cause mortality was 21.5 ng/L, with 72.6% sensitivity and 69.9% specificity (area under the curve: 0.760, 95% CI: 0.692-0.828, P < 0.001). Patients were compared according to the 21.5 ng/L high-sensitivity troponin T cut-off value. At 30-month follow-up, all-cause mortality was 29.3%. According to the Kaplan-Meier analysis, the mortality rate was 14% in the high-sensitivity troponin T < 21.5 ng/L group, while the mortality rate was 50% in the high-sensitivity troponin T ≥ 21.5 ng/L group (P < 0.001, log-rank test). Baseline high-sensitivity troponin T was inde-pendently associated with all-cause mortality in nonischemic heart failure with reduced ejection fraction when adjusted for estimated glomerular filtration rate, hemoglobin, N-terminal pro-brain natriuretic peptide, body mass index, and left atrial diameter (hazard ratio: 1.012, 95% confidence interval: 1.003-1.020, P = 0.005). CONCLUSION: The high-sensitivity troponin T cut-off value was 21.5 ng/L to predict a worse prognosis in nonischemic heart failure with reduced ejection fraction. There was an independent association between high-sensitivity troponin T and all-cause mortality.

Prognostic Significance of Statins in Ischemic and Non-ischemic Heart Failure Patients with Reduced Ejection Fraction in Real Life.

OBJECTIVE: Although the positive effects of statin therapy in cardiovascular diseases are known, current heart failure guidelines do not recommend statins. The aim of this study was to investigate the effect of statin on all-cause mortality in patients with ischemic or non-ischemic heart failure with low ejection fraction using real-life data. METHODS: In this study, 1144 patients with heart failure with low ejection fraction were included retrospectively. RESULTS: In the study cohort, 55.4% were ischemic heart failure patients and 42.4% of the patients were on statin therapy. The rate of patients using statins was 60.5% in the ischemic group and 20.2% in the non-ischemic group (P <.001). During the median 35-month follow-up, 337 deaths were observed. Mortality rates were similar in ischemic and non-ischemic groups (31.3% vs 26.9%, P =.092). When the statin usage status of the patients was examined, ischemic heart failure, all survivors, and survivors with ischemic heart failure were using statins at a higher rate (P <.001). In the Kaplan-Meier analysis of all patients, the mortality rate was 22.7% in statin users, while the mortality rate was significantly higher in those who did not use statins, 34.4% (P <001). All-cause mortality was significantly higher in patients with ischemic heart failure not using statins than in patients using statins (P <.001) but not in non-ischemic heart failure (P =.07). Using statin was an independent predictor of all-cause mortality in all patients (hazard ratio: 0.661, 95% CI: 0.518-0.843, P =.001) and ischemic heart failure patients (hazard ratio: 0.618, 95% CI: 0.456-0.838, P =.002). CONCLUSION: Since statin use reduces all-cause mortality in patients with ischemic heart failure, it may be recommended to continue statin therapy.

Vitamin D Deficiency and Relation to the New York Heart Association Functional Class in Chronic Heart Failure.

OBJECTIVE: Heart failure is an important mortality and morbidity. In this study, we aimed to investigate the frequency of vitamin D deficiency in chronic heart failure patients who live in a sunny region and to evaluate its relationship with the New York Heart Association (NYHA) functional classes. METHODS: The study included 657 patients. Demographic clinical, and laboratory parameters were evaluated according to the NYHA classes. Ordinal regression analysis was used to determine the parameters defining the NYHA class. RESULTS: The median serum 25-hydroxy-vitamin D [25(OH)D] level of study population was 16.88 ng/mL. It was 30 ng/mL. 25(OH)D level was positively correlated with eGFR, calcium, albumin, hemoglobin, transferrin saturation, serum iron, while a negative correlation was found with heart rate, parathormon, NT-proBNP, and CRP. Together with dereased ß blocker use, increase in N-terminal pro-brain natriuretic peptide levels and left atrial diameter, a decrease in vitamin D level (OR: 0.970, 95% CI: 0.945-0996, P=.024) was independently associated with an increase in the New York Heart Association class. CONCLUSION: Vitamin D deficiency and insufficiency are common in patients with chronic heart failure, and vitamin D level is an important determinant of the NYHA functional class in patients with heart failure.

Prognostic value of the combination of uric acid and NT-proBNP in patients with chronic heart failure.

OBJECTIVE: Hyperuricemia is associated with poor outcomes in chronic heart failure (HF). We aimed to evaluate whether uric acid (UA) alone or in combination with N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a good predictor of all-cause mortality, HF hospitalization, and the composite endpoint of HF hospitalization or all-cause mortality in chronic HF. METHODS: UA and NT-proBNP levels were evaluated retrospectively in 861 chronic HF patients with a left ventricular ejection fraction of ≤50%. The patients were compared by dividing them into 4 groups according to the cut-off values of UA and NT-proBNP. RESULTS: Serum UA concentrations were ≥ 7.0 mg/dL in 46.5% of the subjects. With a median follow-up of 30 months, 201 (23.3%) patients died and 308 (35.8%) patients were hospitalized during the study. The all-cause mortality rate was higher in the hyperuricemic group than that of the normouricemic group (p < 0.001). A multivariate Cox regression model revealed that UA and NT-proBNP were independent predictors of all-cause mortality (HR: 1.105, 95% CI: 1.019-1.198, p = 0.016 and HR: 3.743, CI: 2.647-5.292, p < 0.001, respectively). Patients were divided into 4 groups based on UA (≥ 7 and < 7 mg/dL) and NT-proBNP (≥ 2279 and < 2279 ng/L) levels. All-cause mortality, HF hospitalization, and the composite endpoint of HF hospitalization or all-cause mortality rates were higher in the group with high UA and NT-proBNP levels (p < 0.001, p < 0.001, p < 0.001, respectively). CONCLUSION: Hyperuricemia alone is an independent predictor of all-cause mortality in chronic HF. However, the combination of UA and NT-proBNP appears to be a stronger predictor of poor outcomes.

Gender-related clinical and management differences in patients with chronic heart failure with reduced ejection fraction.

AIM: Gender-related differences have been described in the clinical characteristics and management of patients with chronic heart failure with reduced ejection fraction (HFrEF). However, published data are conflictive in this regard. METHODS: We investigated differences in clinical and management variables between male and female patients from the ATA study, a prospective, multicentre, observational study that included 1462 outpatients with chronic HFrEF between January and June 2019. RESULTS: Study population was predominantly male (70.1%). In comparison to men, women with chronic HFrEF were older (66 ± 11 years vs 69 ± 12 years, P < .001), suffered more hospitalisations and presented more frequently with NYHA class III or IV symptoms. Ischaemic heart disease was more frequent in men, whereas anaemia, thyroid disease and depression were more frequent in women. No difference was seen between genders in the use rate of renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, or ivabradine, or in the proportion of patients achieving target doses of these drugs. Regarding device therapies, men were more often treated with an implantable cardioverter-defibrillator (ICD) and women received more cardiac resynchronisation therapy. CONCLUSION: In summary, although management seemed to be equivalent between genders, women tended to present with more symptoms, require hospitalisation more frequently and have different comorbidities than men. These results highlight the importance of gender-related differences in HFrEF and call for further research to clarify the causes of these disparities. Gender-specific recommendations should be included in future guidelines in HFrEF.

Adherence to guideline-directed medical and device Therapy in outpAtients with heart failure with reduced ejection fraction: The ATA study.

OBJECTIVE: Despite recommendations from heart failure guidelines on the use of pharmacologic and device therapy in patients with heart failure with reduced ejection fraction (HFrEF), important inconsistencies in guideline adherence persist in practice. The aim of this study was to assess adherence to guideline-directed medical and device therapy for the treatment of patients with chronic HFrEF (left ventricular ejection fraction ≤40%). METHODS: The Adherence to guideline-directed medical and device Therapy in outpAtients with HFrEF (ATA) study is a prospective, multicenter, observational study conducted in 24 centers from January 2019 to June 2019. RESULTS: The study included 1462 outpatients (male: 70.1%, mean age: 67±11 years, mean LVEF: 30%±6%) with chronic HFrEF. Renin-angiotensin system (RAS) inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and ivabradin were used in 78.2%, 90.2%, 55.4%, and 12.1% of patients, respectively. The proportion of patients receiving target doses of medical treatments was 24.6% for RAS inhibitors, 9.9% for beta-blockers, and 10.5% for MRAs. Among patients who met the criteria for implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy (CRT), only 16.9% of patients received an ICD (167 of 983) and 34% (95 of 279) of patients underwent CRT (95 of 279). CONCLUSION: The ATA study shows that most HFrEF outpatients receive RAS inhibitors and beta-blockers but not MRAs or ivabradin when the medical reasons for nonuse, such as drug intolerance or contraindications, are taken into account. In addition, most eligible patients with HFrEF do not receive target doses of pharmacological treatments or guideline-recommended device therapy.

Echocardiographic assessment of right ventricular function in peritoneal dialysis patients.

OBJECTIVE: Cardiovascular disease is the leading cause of mortality in patients undergoing dialysis. Most of the available studies focus on left ventricular (LV) function in peritoneal dialysis (PD) patients; data about the effect of PD on right ventricular (RV) function are scarce. The aim of this study was to evaluate echocardiographic parameters of the RV in patients with end-stage renal disease (ESRD) undergoing PD. METHODS: A total of 73 individuals were grouped as follows: PD patients (n=36) and healthy controls (n=37). Echocardiography of the RV was performed in all of the patients using tissue Doppler imaging (TDI). RESULTS: The LV mass index (LVMI), left atrial (LA) diameter, posterior wall, and interventricular septum thicknesses were significantly greater in the PD group. The LV peak late diastolic atrial contraction (A) velocity was higher, and the peak early diastolic (E) velocity and the early diastolic velocity of the lateral mitral annulus (Em) were lower in the PD group compared with the control group. The right atrial (RA) diameter, RA area, RV fractional area change, RV myocardial performance index, and pulmonary vascular resistance values were similar in both groups, whereas the tricuspid annular plane systolic excursion (TAPSE) value was lower in the PD patients. The RV E; early diastolic (Ea), late diastolic (Aa), and systolic (Sa) velocities; deceleration time; and tricuspid regurgitation velocity were also similar in the 2 groups. Only the RV A velocity and the Ea/Aa ratio were significantly higher in the PD group, and the E/A ratio was lower in the PD group than in the control group. CONCLUSION: The results of conventional and TDI echocardiography indicated that RV systolic and diastolic functions were preserved in PD patients.