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.

Rationale, Design, and Methodology of the MORCOR-TURK Trial: Predictors of In-hospital MORtality in CORonary Care Patients in Turkey.

BACKGROUND: Coronary care units are sophisticated clinics established to reduce deaths due to acute cardiovascular events. Current data on coronary care unit mortality rates and predictors of mortality in Turkey are very limited. The MORtality predictors in CORonary care units in TURKey (MORCOR-TURK) trial was designed to provide information on the mortality rates and predictors in patients followed in coronary care units in Turkey. METHODS: The MORCOR-TURK trial will be a national, observational, multicenter, and noninterventional study conducted in Turkey. The study population will include coronary care unit patients from 50 centers selected from all regions in Turkey. All consecutive patients admitted to coronary care units with cardiovascular diagnoses between 1 and 30 September 2022 will be prospectively enrolled. All data will be collected at one point in time, and the current clinical practice will be evaluated (ClinicalTrials.gov number NCT05296694). In the first step of the study, admission diagnoses, demographic characteristics, basic clinical and laboratory data, and in-hospital management will be assessed. At the end of the first step, the predictors and rates of in-hospital mortality will be documented. The second step will be in cohort design, and discharged patients will be followed up till 1 year. Predictors of short- and long-term mortality will be assessed. Moreover, a new coronary care unit mortality score will be generated with data acquired from this cohort. RESULTS: The short-term outcomes of the study are planned to be shared by early 2023. CONCLUSION: The MORCOR-TURK trial will be the largest and most comprehensive study in Turkey evaluating the rates and predictors of in-hospital mortality of patients admitted to coronary care units.

The Safety and Tolerability of Nebivolol in Hypertensive Patients with Coronary Artery Disease and Left Ventricular Ejection Fraction ≥ 40%: A Population-Based Cohort Study (Nebivolol-TR Study).

BACKGROUND: This study aimed to assess the safety and tolerability of nebivolol in hypertensive patients with coronary artery disease and left ventricular ejection fraction ≥ 40% in a Turkish cohort. METHODS: A total of 1015 hypertensive patients and coronary artery disease with left ventricular ejection fraction ≥ 40% were analyzed from 29 different centers in Turkey. Primary outcomes were the mean change in blood pressure and heart rate. Secondary outcomes were to assess the rate of reaching targeted blood pressure (<130/80 mmHg) and heart rate (<60 bpm) and the changes in the clinical symptoms (angina and dyspnea). Adverse clinical events and clinical outcomes including cardiovascular mortality, cardiovascular hospital admissions, or acute cardiac event were recorded. RESULTS: The mean age of the study population was 60.3 ± 11.5 years (male: 54.2%). During a mean follow-up of 6 months, the mean change in blood pressure was -11.2 ± 23.5/-5.1 ± 13.5 mmHg, and the resting heart rate was -12.1 ± 3.5 bpm. Target blood pressure and heart rate were achieved in 76.5% and 37.7% of patients. Angina and functional classifications were improved by at least 1 or more categories in 31% and 23.2% of patients. No serious adverse events related to nebivolol were reported. The most common cardiovascular side effect was symptomatic hypotension (4.2%). The discontinuation rate was 1.7%. Cardiovascular hospital admission rate was 5% and hospitalization due to heart failure was 1.9% during 6 months' follow-up. Cardiovascular mortality rate was 0.1%. CONCLUSION: Nebivolol was well tolerated and safe for achieving blood pressure and heart rate control in hypertensive patients with coronary artery disease and heart failure with preserved or mildly reduced ejection fraction.

Comparison of long-term outcome of patients with ST-segment elevation myocardial infarction between pre-COVID-19 and COVID-19 era.

AIMS: To compare major cardiovascular and cerebrovascular events (MACCE) rates between patients in the pre-COVID-19 era and COVID-19 era, and to assess the impact of the presence of COVID-19 (+) on long-term MACCE in ST-segment elevation myocardial infarction (STEMI) in Turkey. METHODS: Using the TURSER study (TURKISH ST-segment elevation myocardial infarction registry) data, the current study included 1748 STEMI patients from 15 centres in Turkey. Patients were stratified into COVID-19 era (March 11st-May 15st, 2020; n = 723) or pre-COVID-19 era (March 11st-May 15st, 2019; n = 1025) cohorts. Long-term MACCE rates were compared between groups. In addition, the effect of COVID-19 positivity on long-term outcomes was evaluated. The primary outcome was the occurrence of MACCE at long-term follow-up, and the secondary outcome was hospitalization with heart failure. RESULTS: The MACCE and hospitalization with heart failure rates between pre-COVID-19 era and COVID-19 era were 23% versus 22% (p = .841), and 12% versus 8% (p = .002), respectively. In the COVID-19 era, the rates of MACCE and hospitalization with heart failure COVID-19-positive versus COVID-19-negative patients were 40% versus 20%, (p < .001), and 43% versus 11% (p < .001), respectively. CONCLUSION: There was no difference between the pre-COVID-19 era and the COVID-19 era in terms of MACCE  in STEMI patients in Turkey. In the COVID-19 era, STEMI patients positive for COVID-19 had a higher rate of MACCE and heart failure hospitalization at the long-term follow-up.

Impact of COVID-19 outbreak on patients with ST-segment elevation myocardial infarction (STEMI) in Turkey: results from TURSER study (TURKISH St-segment elevation myocardial infarction registry).

OBJECTIVE: We aimed to investigate both the impact of COVID-19 pandemic on ST-segment elevation myocardial infarction (STEMI) admission, and demographic, angiographic, procedural characteristics, and in-hospital clinical outcomes of patients with COVID-19 positive STEMI in Turkey. METHODS: This was a multi-center and cross-sectional observational study. The study population included 1788 STEMI patients from 15 centers in Turkey. The patients were divided into two groups: COVID-19 era (March 11st-May 15st, 2020; n = 733) or pre- COVID-19 era group (March 11st-May 15st, 2019; n = 1055). Also, the patients in COVID-19 era were grouped as COVID-19 positive (n = 65) or negative (n = 668). RESULTS: There was a 30.5% drop in STEMI admission during COVID-19 era in comparison to pre-COVID-19 era. The patients admitted to the medical centers during COVID-19 era had a longer symptom-to-first medical contact time [120 (75-240) vs. 100 (60-180) minutes, p < 0.001]. COVID-19 positive STEMI patients had higher thrombus grade and lower left ventricular ejection fraction compared to COVID-19 negative patients. COVID-19 positive patients had higher mortality (28% vs. 6%, p < 0.001) and cardiogenic shock (20% vs. 7%, p < 0.001) rates compared with those without COVID-19. Matching based on propensity scores showed higher mortality and high thrombus grade in STEMI patients who were infected by SARS-COV-2 (each p < 0.05). CONCLUSIONS: We detected significantly lower STEMI hospitalization rates and significant delay in duration of symptom onset to first medical contact in the context of Turkey during the COVID-19 outbreak. Moreover, high thrombus grade and mortality were more common in COVID-19 positive STEMI patients.

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.