Right heart failure with left ventricular assist devices: Preoperative, perioperative and postoperative management strategies. A clinical consensus statement of the Heart Failure Association (HFA) of the ESC.

Right heart failure (RHF) following implantation of a left ventricular assist device (LVAD) is a common and potentially serious condition with a wide spectrum of clinical presentations with an unfavourable effect on patient outcomes. Clinical scores that predict the occurrence of right ventricular (RV) failure have included multiple clinical, biochemical, imaging and haemodynamic parameters. However, unless the right ventricle is overtly dysfunctional with end-organ involvement, prediction of RHF post-LVAD implantation is, in most cases, difficult and inaccurate. For these reasons optimization of RV function in every patient is a reasonable practice aiming at preparing the right ventricle for a new and challenging haemodynamic environment after LVAD implantation. To this end, the institution of diuretics, inotropes and even temporary mechanical circulatory support may improve RV function, thereby preparing it for a better adaptation post-LVAD implantation. Furthermore, meticulous management of patients during the perioperative and immediate postoperative period should facilitate identification of RV failure refractory to medication. When RHF occurs late during chronic LVAD support, this is associated with worse long-term outcomes. Careful monitoring of RV function and characterization of the origination deficit should therefore continue throughout the patient's entire follow-up. Despite the useful information provided by the echocardiogram with respect to RV function, right heart catheterization frequently offers additional support for the assessment and optimization of RV function in LVAD-supported patients. In any patient candidate for LVAD therapy, evaluation and treatment of RV function and failure should be assessed in a multidimensional and multidisciplinary manner.

Patient Perception, Knowledge and Adaptation in The Management of Heart Failure: A Multicenter, Cross-Sectional, Observational, Questionnaire-Based Study: ADAPTATION HF.

OBJECTIVE: The aim of this study is to reveal the perception levels of heart failure (HF) patients about the disease, their adaptation to the disease process, their compliance with the treatment, and their knowledge and thoughts about the disease from the patient's perspective. METHOD: Patients with a diagnosis of HF for at least 6 months who applied to the cardiology clinics of 10 different centers were included in this cross-sectional, multicenter and questionnaire-based study. A questionnaire consisting of sections that included demographic information, evaluation of the patient's symptoms, knowledge and experience of clinical follow-up, knowledge of HF, compliance and awareness of treatment was applied to the patients. RESULTS: 504 patients with a mean age of 59.8 ± 14.9 years (M/F: 360/144, 71.4%/28.6%) were included in the study. 61.2% of the patients stated that they knew about HF disease before. Most of the patients knew that the complaints of shortness of breath, fatigue and palpitation could develop due to HF (95.4%; 92.7%; 89.7%, respectively). The patients reported that they were mostly worried about not being able to provide their own self-care without the support of another person (67.5%). While the majority of patients (37.6%) thought that the worst disease was to have a cerebrovascular disease; only 10.9% stated that HF was the worst disease. While 98.8% of the patients stated that they used HF drugs regularly, a relatively large part of the patients did not know that the drugs were effective on kidney functions (68.5%) and blood pressure (76.9%). In the daily practice of the patients, the rate of weight follow-up was 35.5%, the rate of blood pressure monitoring was 26.9%, and the rate of patients who exercised was 27%. Among the patients, 73.3% said that they pay attention to the amount of salt they take with diet, and 33.5% have a completely salt.free diet. There was no difference between the groups with low and high knowledge scores in terms of Pittsburgh Sleep Quality Index (P > 0.005). The knowledge level score was significantly higher in patients with previous myocardial infarction (P = 0.002). CONCLUSION: Most of the HF patients participating in the study are aware of the signs and symptoms of HF, follow the recommendations of their physicians, and use drugs regularly. These patients should have more information about blood pressure monitoring, weight monitoring, diet and sodium restriction, exercise, which are included in the non-pharmacological part of treatment management.

Impact of the empirical therapy timing on the clinical progress of septic shock patients.

AIM: To evaluate the effect of timing of antimicrobial therapy on clinical progress of patients with septic shock. MATERIALS AND METHOD: We included 204 adult patients diagnosed with septic shock according to Sepsis-3 criteria between March 2016 and April 2021. One-month survival was evaluated using univariate and logistic regression analysis. RESULTS: Antibiotic treatment was initiated within 1 h of the vasopressors in 26.4 % of patients. One-month mortality did not differ significantly between patients with and without empirical therapy coverage on etiological agents. Univariate factors that significantly affected one-month survival were starting antibiotics at the first hour, the unit where the case was diagnosed with septic shock, SOFA scores, qSOFA scores, and lactate level. In multivariate analysis, diagnosis of septic shock in the Emergency Service, SOFA score ≥11, qSOFA score of three and lactate level ≥4 were significantly associated with one-month mortality. CONCLUSION: Training programs should be designed to increase the awareness of septic shock diagnosis and treatment in the Emergency Service and other hospital units. Additionally, electronic patient files should have warning systems for earlier diagnosis and consultation.

Antibody Response to SARS-CoV-2 Vaccination in Heart Failure Patients: Retrospective Single-Center Cohort Study.

We sought to investigate the impact of heart failure on anti-spike antibody positivity following SARS-CoV-2 vaccination. Our study included 103 heart failure (HF) patients, including those with and without left ventricular assist devices (LVAD) selected from our institutional transplant waiting list as well as 104 non-heart failure (NHF) patients who underwent open heart surgery at our institution from 2021 to 2022. All the patients received either heterologous or homologous doses of BNT162b2 and CoronaVac. The median age of the HF group was 56.0 (interquartile range (IQR): 48.0-62.5) and the NHF group was 63.0 (IQR: 56.0-70.2) years, and the majority were males in both groups (n = 78; 75.7% and n = 80; 76.9%, respectively). The majority of the patients in both the HF and NHF groups received heterologous vaccinations (n = 43; 41.7% and n = 52; 50.3%, respectively; p = 0.002). There was no difference in the anti-spike antibody positivity between the patients with and without heart failure (p = 0.725). Vaccination with BNT162b2 led to significantly higher antibody levels compared to CoronaVac alone (OR: 11.0; 95% CI: 3.8-31.5). With each passing day after the last vaccine dose, there was a significant decrease in anti-spike antibody positivity, with an OR of 0.9 (95% CI: 0.9-0.9). Furthermore, hyperlipidemia was associated with increased antibody positivity (p = 0.004).

Trends in heart failure between 2016 and 2022 in Türkiye (TRends-HF): a nationwide retrospective cohort study of 85 million individuals across entire population of all ages.

Background: Data on the burden of heart failure (HF) outside western countries are limited, but available data suggest it may present differently in other countries. The aim of this study was to examine the incidence, prevalence, and survival rates of HF in Türkiye, with a specific focus on how these rates vary according to age, sex, comorbidities, and socioeconomic status (SES). Methods: We harnessed the extensive National Electronic Database of the Turkish Ministry of Health, covering Turkey's entire population from January 1, 2016, to December 31, 2022, to identify 2,722,151 cases of HF and their associated comorbidities using ICD-10 codes. Analyzing the primary endpoint of all-cause mortality, our study utilized anonymized data to examine patient demographics, comorbidities, socioeconomic status, and survival patterns, employing statistical techniques to delve into relationships and trends. The data were segmented by gender, socioeconomic status, and age, involving cross-tabulations and statistical metrics to explore connections, odds ratios, and survival rates. Findings: The estimated prevalence of HF was 2.114% in Türkiye at the end of 2022, with an annual incidence ranging between 3.00 and 6.06 per 1000 person years. Females were older than males (69.8 ± 13.9 years vs. 66.8 ± 13.9 years, respectively). The most common comorbidities were congenital heart diseases and anemia under the age of 20, and hypertension and atherosclerotic cardiovascular disease in the adult population. Only 23.6% (643,159/2,722,151) of patients were treated with any triple guideline-directed medical therapy (GDMT) and 3.6% (96,751/2,722,151) of patients were on quadruple GDMT. The survival rates for patients with HF at 1, 5, and 7 years were 83.3% (95% CI: 83.2-83.3), 61.5% (95% CI: 61.4-61.6), and 57.7% (95% CI: 57.6-57.8) among females, and 82.1% (95% CI: 82.0-82.2), 58.2% (95% CI: 58.1-58.3), and 54.2% (95% CI: 54.0-54.3) among males. Despite a tendency for an increase from the highest to the lowest SES, the prevalence of HF and mortality were paradoxically lowest in the lowest SES region. Interpretation: The prevalence, incidence, and survival rates of HF in Türkiye were comparable to western countries, despite the notable difference of HF onset occurring 8-10 years earlier in the Turkish population. Drug usage statistics indicate there is a need for effective strategies to improve treatment with GDMT. Funding: None.

Long-Term Natural Course of Patients with Pulmonary Artery Pressures in the Range of 21-24 mmHg: Insights from a Single-Center Study.

OBJECTIVE: Slightly elevated mean pulmonary artery pressure (mPAP) was previously termed as ''borderline pulmonary hypertension (PH)''. We examined the long-term prognosis of patients with mPAP values between 21 and 24 mmHg, who were referred with the suspicion of pulmonary hypertension. METHODS: Our retrospective study included patients with moderate-to-high echocardiographic risk who underwent right heart catheterization (RHC) between 2008 and 2021 and were followed for at least 1 year. Patients with mPAP <21 mmHg and mPAP 21-24 mmHg were compared. Demographic and clinical characteristics and prognoses of the groups were compared. All-cause mortality over a mean follow-up of 5 years (min 1-max 13 years) was evaluated. RESULTS: A total of 140 patients (mean age 53.1 ± 14.8 years, female 74.5%) with mPAP values <25 mmHg measured of the 395 diagnostic RHCs. Mean follow-up was 4.92 ± 3.13 years. NT-pro-BNP and 6-min walking distance were better in patients with mPAP <21 mmHg. Echocardiographic findings suggestive of PH were more common in mPAP 21-24 mmHg group (P < 0.05). Both the pulmonary artery wedge pressure and cardiac index values were significantly deteriorated in individuals with mPAP 21-24 mmHg (P = 0.001). All-cause mortality tended to be higher in the borderline PH group but did not reach to statistical significance. CONCLUSION: Our single-center observational study revealed that the individuals with an mPAP of 21-24 mmHg tended to have a worser prognosis than those with mPAP of <21 mmHg for up to 13-year follow-up.

Could Heart Rate Variability Serve as a Prognostic Factor in Patients with Pulmonary Hypertension? A Single-center Pilot Study.

OBJECTIVE: Heart rate variability (HRV), which is defined as cyclic changes in sinus rate with time, is used as a measure of cardiac autonomic tone. Our aim was to determine the impact of HRV on short-term prognosis in pulmonary hypertension (PH). METHODS: We enrolled 64 PH patients and 69 healthy subjects (control group). Patients were evaluated by Holter-ECG, echocardiography, and laboratory tests. 24-h Holter-ECG monitoring was used for HRV. The development of adverse events (right heart failure, hospitalization, syncope, and death) during the 6-month follow-up was evaluated in PH group. RESULTS: PH group (39 ± 16 years, 37.5% males) comprised of 16 patients with idiopathic pulmonary arterial hypertension (PAH) (25%), 36 patients with PAH associated with congenital heart disease (56.3%), 3 PAH associated with connective tissue disease (4.7%), 1 with portopulmonary (1.6%), and 8 chronic thromboembolic PH (12.5%). The time-dependent (standard deviation of all NN intervals for a selected time period [SDNN], standard deviation of the 5-min mean R-R intervals tabulated over an entire day [SDANN], SDNN Index, and Triangular Index) and frequency-dependent HRV indices (low frequency, high-frequency power, and total power,) were significantly reduced in those with PH. Functional class was negatively associated with SDNN, SDANN, SDNN Index, and Triangular Index. Adverse events developed in 25% of the patients during the 6-month follow-up period (200 ± 92 days) (7 patients had right-heart failure, 5 syncope, 12 patients were hospitalized, and 9 had died). All the time and frequency-dependent indices significantly associated with adverse events. Mortality correlated with SDNN (rS = -0.354, P = 0.005), SDANN (rS = -0.368, P = 0.004), SDNN Index (rS = -0.257, P = 0.045), Triangular Index (rS = -0.310, P = 0.014), and VLF (rS = -0.265, P = 0.039). CONCLUSION: HRV is significantly depressed in patients with PH and is associated with the clinical status. HRV indices might predict clinical deterioration, adverse events, and mortality for 6 months. Non-invasive assessment of HRV through Holter-ECG may be a valuable and practical tool in risk stratification of patients with PH for short-term outcomes.

Effect of Aortic Valve Opening Pattern on Endothelial Function After Continuous-Flow Left Ventricular Assist Device Implantation.

This study aimed to evaluate the effects of aortic valve opening patterns on endothelial functions in patients undergoing continuous-flow left ventricular assist device (CF-LVAD) implantation. This study included 43 patients who underwent CF-LVAD implantation and 35 patients with heart failure reduced ejection fraction (HFrEF; control group). The CF-LVAD group was divided into three subgroups based on aortic valve opening patterns: open with each beat, intermittently opening, and not opening groups. Flow-mediated dilatation (FMD) and pulsatility index (PI) were compared before and 3 months after CF-LVAD implantation. Cardiopulmonary exercise test (CPET) and 6 minute walk test (6-MWT) scores were measured at baseline and follow-up in the CF-LVAD group. The mean FMD and PI of patients in the CF-LVAD group reduced 3 months after implantation. Patients with intermittently opening and not opening aortic valves had worse endothelial function at follow-up. Before and 3 months after implantation FMD% did not significantly differ in patients whose aortic valves were open with each beat (4.72 ± 1.06% vs. 4.67 ± 1.16%, p = 0.135). Pulsatility index changes paralleled FMD changes. Cardiopulmonary exercise test and 6-MWT scores improved after implantation but without significant differences between subgroups. Maintaining normal aortic valve function after CF-LVAD implantation may reduce endothelial dysfunction; however, larger studies are needed for long-term clinical effects.

Could Impedance Cardiography be a Non-Invasive Alternative Method of Measuring Cardiac Output in Patients with Pulmonary Hypertension?

BACKGROUND: Pulmonary hypertension guidelines recommend invasive right heart catheterization for diagnosis and clinical follow-up. Our aim was to compare non-invasive impedance cardiography with invasive techniques for cardiac index measurements and mortality prediction in patients with pulmonary hypertension. METHODS: Between 2008 and 2018, 284 right heart catheterizations were performed for the diagnosis of pulmonary hypertension in 215 patients with mean pulmonary artery pressure >25 mm Hg, and at least 2 methods used for cardiac output measurement were included in the study retrospectively. Patients were evaluated with Pearson's correlation in 3 groups: estimated Fick (eFick) method and thermodilution (group 1), eFick method and impedance cardiography (group 2), and thermodilution and impedance cardiography (group 3). We also compared the predictive power of cardiac index measured by different methods for 1-year overall mortality and hospitalizations. RESULTS: There were strong and moderate positive correlations in groups 1 and 3, respectively (r = 0.634, P <.001, r = 0.534, P =.001), and the weakest correlation was in group 2 (r = 0.390, P =.001). The mean difference (bias) between eFick method versus impedance cardiography, impedance cardiography vs. thermodilution, and eFick method vs. thermodilution was 0.6 mL/min, 0.47 mL/min, and -0.2 mL/min respectively, but limits of agreement were wide. In both groups, cardiac index <2.5 L/min/m2 as measured by thermodilution significantly predicted 1-year mortality. Also, impedance cardiography was better than eFick method in predicting mortality (P =.02). CONCLUSIONS: Our single-center real-life data showed that for cardiac output and cardiac index measurements, impedance cardiography provides a moderate correlation with thermodilution and is fair with eFick method methods. Moreover, thermodilution appeared superior to both eFick method and impedance cardiography, while impedance cardiography was even better than eFick method in predicting 1-year adverse events, including total mortality and hospitalization, in patients with pulmonary hypertension.

Risk Assessment Tool Implementation in Congenital Heart Disease-Associated Pulmonary Arterial Hypertension.

BACKGROUND: Risk assessment is recommended for patients with congenital heart disease-associated pulmonary arterial hypertension. This study aims to compare an abbreviated version of the risk assessment strategy, noninvasive French model, and an abridged version of the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management 2.0 risk score calculator, Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management Lite 2. METHODS: We enrolled a mixed prevalent and incident cohort of patients with congenital heart disease-associated pulmonary arterial hypertension (n = 126). Noninvasive French model comprising World Health Organization functional class, 6-minute walk distance, and N-terminal pro-hormone of brain natriuretic peptide or brain natriuretic peptide was used. Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management Lite 2 includes functional class, systolic blood pressure, heart rate, 6-minute walk distance, brain natriuretic peptide/N-terminal pro-hormone of brain natriuretic peptide, and estimated glomerular filtration rate. RESULTS: The mean age was 32.17 ± 16.3 years. The mean follow-up was 99.41 ± 58.2 months. Thirty-two patients died during follow-up period. Most patients were Eisenmenger syndrome (31%) and simple defects (29.4%). Most patients received monotherapy (76.2%). Most patients were World Health Organization functional class I-II (66.6%). Both models effectively identified risk in our cohort (P =.0001). Patients achieving 2 or 3 noninva-sive low-risk criteria or low-risk category by Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management Lite 2 at follow-up had a significantly reduced risk of death. Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management Lite 2 approximates noninvasive French model at discriminating among patients based on c-index. Age, high risk by Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management Lite 2, and the presence of 2 or 3 low-risk criteria by noninvasive French model emerged as an independent predictors of mortality (multivariate hazard ratio: 1.031, 95% CI: 1.005-1.058, P =.02; hazard ratio: 4.258, CI: 1.143-15.860, P =.031; hazard ratio: 0.095, CI: 0.013-0.672, P =.018, respectively). CONCLUSIONS: Both abbreviated risk assessment tools may provide a simplified and robust method of risk assessment for congenital heart disease-associated pulmonary arterial hypertension. Patients not achieving low risk at follow-up may benefit from aggressive use of available therapies.

Decreased circulating microRNA-21 and microRNA-143 are associated to pulmonary hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by maladaptation of pulmonary vasculature which is leading to right ventricular hypertrophy and heart failure. miRNAs play a crucial role in the regulation of many diseases such as viral infection, cancer, cardiovascular diseases, and pulmonary hypertension (PH). In this study, we aimed to investigate the expression pattern of eight human plasma miRNAs (hsa-miR-21-3p, hsa-miR-143- 3p, hsa-miR-138-5p, hsa-miR-145-3p, hsa-miR-190a, hsa-miR-204-3p, hsamiR-206, hsa-miR-210-3p) in mild-to-severe PH patients and healthy controls. METHODS: : miRNAs were extracted from the peripheral plasma of the PH patients (n: 44) and healthy individuals (n: 30) by using the miRNA Isolation Kit. cDNA was synthesized using All in-One First strand cDNA Synthesis Kit. Expression of the human plasma hsa-miR- 21-3p, hsa-miR-143-3p, hsa-miR-138-5p, hsa-miR-145-3p, hsa-miR-190a, hsa-miR-204- 3p, hsa-miR-206, hsa-miR210-3p, and miRNAs were analyzed by qRT-PCR. RESULTS: According to our results, in PH patients hsa-miR-21-3p and hsa-miR-143-3p expression levels were decreased by 4.7 and 2.3 times, respectively. No significant changes were detected in hsa-miR-138-5p, hsa-miR-145-3p, hsa-miR-190a, hsa-miR-204-3p, hsamiR-206, and hsa-miR-210-3p expression levels between PH and control groups. In addition, considering the severity of the disease, it was observed that the decrease in miR-138, miR-143, miR-145, miR-190, mir-204, mir-206 and miR-208 expressions was significant in patients with severe PH. DISCUSSION: : In the early diagnosis of PAH, hsa-miR-21-3p and especially hsa-miR-143-3p in peripheral plasma can be considered as potential biomarkers.

Inotropic therapy in patients with advanced heart failure. A clinical consensus statement from the Heart Failure Association of the European Society of Cardiology.

This clinical consensus statement reviews the use of inotropic support in patients with advanced heart failure. The current guidelines only support use of inotropes in the setting of acute decompensated heart failure with evidence of organ malperfusion or shock. However, inotropic support may be reasonable in other patients with advanced heart failure without acute severe decompensation. The clinical evidence supporting use of inotropes in these situations is reviewed. Particularly, patients with persistent congestion, systemic hypoperfusion, or advanced heart failure with need for palliation, and specific situations relevant to implantation of left ventricular assist devices or heart transplantation are discussed. Traditional and novel drugs with inotropic effects are discussed and use of guideline-directed therapy during inotropic support is reviewed. Finally, home inotropic therapy is described, and palliative care and end-of-life aspects are reviewed in relation to management of ongoing inotropic support (including guidance for maintenance and weaning of chronic inotropic therapy support).

The outcome of peripartum cardiomyopathy patients-single center experience.

OBJECTIVE: Peripartum cardiomyopathy (PPCM) diagnosis made by excluding identifiable causes of heart failure (HF) and occurs end of the pregnancy or during the postpartum period of five months. It presents a clinical HF spectrum with left ventricular systolic dysfunction. BACKGROUND: The purpose of this study is to retrospectively evaluate the clinical characteristics, cardiac magnetic resonance (CMR) imaging features, and end-points consisting of left ventricle recovery, left ventricular assist device implantation, heart transplantation, and all-cause mortality. METHOD: Outpatient HF records between 2008 to 2021 were screened. Thirty-seven patients were defined as PPCM. Twenty-five patients had CMR evaluation at the time of diagnosis, and six patients were re-evaluated with CMR. RESULTS: The mean age was 30.5 ± 5.6 years, and the mean LVEF was 28.2% ± 6.7%. In 13(35.7%) patients, LVEF recovered during the follow-up course. The median recovery time was 281(IQR [78-358]) days. LVEF on CMR was 35.3 ± 10.5, and three patients exhibited late gadolinium enhancement(LGE) patterns. Sub-endocardial and mid-wall uptake pattern types were detected. 18(75%) patients met the Petersen left ventricle non-compaction cardiomyopathy(LVNC) criteria. Patients with NC/C ratio lower than 2.3 had lower LVEDVi and LVESVi (124.9 ± 35.4, 86.4 ± 7.5, p = .003; 86.8 ± 34.6, 52.6 ± 7.6, p = .006), respectively. The median follow-up time was 2129 (IQR [911-2634]) days. The primary endpoint-free 1-year survival was 88.9% (event rate 11.1%), and 5-year survival was 75.7% (event rate 24.3%). CONCLUSION: In a retrospective cohort of PPCM patients, 35.7% of patients' LVEF recovered, and the primary end-point of free-5-year survival was 75%. Twenty-five patients were assessed with CMR; three of four met the Petersen CMR-derived LVNC at initial evaluation.

Outcomes of patients with left ventricular assist device infected with SARS-CoV-2.

Background: The aim of this study was to describe clinical characteristics, course, and outcomes of the novel coronavirus disease 2019 (COVID-19) in heart failure patients with left ventricular assist device. Methods: Between November 2020 and August 2021, a total of 20 patients (18 males, 2 females; mean age: 57.0+10.0 years; range, 30 to 71 years) with left ventricular assist device and who were diagnosed by the COVID-19 polymerase chain reaction testing were included. For each patient, disease-related factors were evaluated including presence of hospitalization, home quarantine, presence of lung damage, antiviral medication strategy, symptomatology and complications following COVID-19. Results: Seven patients 35% patients died in our cohort following the COVID-19. All these patients experienced variety of complications following COVID-19 including subarachnoid hemorrhage and right heart failure. Three patients were already hospitalized due to COVID-19 and decompensated progressively, resulting in death on Days 14, 4, and 7 after the initial diagnosis. Conclusion: COVID-19 seems to be an important cause of mortality in patients with LVAD who have borderline cardiopulmonary function. Great care should be taken to avoid interruption in routine follow-ups with these patients, since they present a more sensitive population.

Characteristics and long-term survival of patients with left ventricular non-compaction cardiomyopathy.

AIMS: Left ventricular non-compaction cardiomyopathy (LVNC) is a poorly understood entity resulting in heart failure. Whether it is a distinct form of cardiomyopathy or an anatomical phenotype is a subject of discussion. The current diagnosis is based on morphologic findings by comparing the compacted to non-compacted myocardium. The study aimed to compare demographic and prognostic variables of patients with dilated cardiomyopathy (DCM) and LVNC. Emphasis was given to cardiac magnetic resonance (CMR) imaging analysis. Data on survival were also assessed. METHODS AND RESULTS: We retrospectively evaluated the characteristics and outcomes of 262 non-ischaemic cardiomyopathy patients with LVNC and DCM phenotypes. Petersen's CMR criteria of non-compacted to the compacted myocardial ratio 2.3 were used to diagnose LVNC. The primary endpoint was a composite endpoint of major adverse cardiovascular events comprising cardiovascular-related death, left ventricular assisted device implantation, or heart transplantation. A total of 262 patients with CMR data were included in the study. One hundred fifty-five patients who fulfilled CMR criteria were diagnosed as LVNC. CMR findings revealed that LVNC patients had higher left ventricular end-diastolic (137.2 ± 51.6, 116.8 ± 44.6, P = 0.002) and systolic volume index (98.4 ± 49.5, 85.9 ± 42.7, P = 0.049). Cardiac haemodynamics, cardiac output (5.61 ± 2.03, 4.96 ± 1.83; P = 0.010), stroke volume (73.9 ± 28.8, 65.1 ± 25.1; P = 0.013), and cardiac index (2.85 ± 1.0, 2.37 ± 0.72; P < 0.0001), were higher in LVNC patients. Of all the 249 patients, 102 (40.9%) patients demonstrated late gadolinium enhancement (LGE). According to Petersen's criteria, the Kaplan-Meier survival outcome did not reveal significant differences (hazard ratio [HR]: 1.53, 95% confidence interval [CI]: [0.89-2.63], P = 0.11). The presence or pattern of LGE did not show significant importance for endpoint-free survival. Most of the sub-epicardial LGE pattern was found in LVNC patients (94.4%). When receiver operator characteristics analysis was applied to NC/C ratio to discriminate the primary endpoint, a higher NC/C ratio of 2.57 was associated with adverse events (HR: 1.90, 95% CI: [1.12-3.24], P = 0.016). CONCLUSIONS: Our study questions the criteria being used for the diagnosis of LVNC. Further evaluation of CMR variables and association of these findings with demographic variables and survival is mandatory.

Heart failure with non-reduced ejection fraction: Epidemiology, pathophysiology, phenotypes, diagnosis and treatment approaches.

Heart failure (HF) has been classified as reduced ejection fraction (HFrEF), mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF) by the recent HF guidelines. In addition, HF with improved ejection fraction has been defined as a subgroup of HFrEF. In HFrEF, diagnostic workup and evidence-based pharmacological and device-based therapies have been well established. However, HFpEF, which comprises almost half of the HF population, represents significant uncertainties regarding its pathophysiology, clinical phenotypes, diagnosis and treatment. Diagnostic criteria of HFpEF have been changed a few times over the years and still remained a matter of debate. New paradigms including a prominent role of co-morbidities, inflammation, endothelial dysfunction have been proposed in its pathophysiology. As a complex, multifactorial syndrome HFpEF consists of many overlapping clinical and hemodynamic phenotypes. In contrast to HFrEF, clinical outcomes of HFpEF have not improved over the last decades due to lack of proven effective therapies. Although HFrEF and HFpEF have different clinical spectrums and proposed pathophysiological mechanisms, there is no clear defining syndrome postulated for HFmrEF. Clinical characteristics and risk factors of HFmrEF overlap with HFrEF and HFpEF. HFmrEF is also referred as a transitional zone for dynamic temporal changes in EF. So, HFpEF and HFmrEF, both namely HF with non-reduced ejection fraction (HF-NEF), have some challenges in the management of HF. The purpose of this paper is to provide a comprehensive review including epidemiology, pathophysiology, clinical presentation and phenotypes of HF-NEF and to guide clinicians for the diagnosis and therapeutic approaches based on the available data in the literature.

Cost-of-disease of Heart Failure in Turkey: A Delphi Panel-based Analysis of Direct and Indirect Costs.

Background: Heart failure (HF) is considered a significant public health issue with a substantial and growing epidemiologic and economic burden in relation to longer life expectancy and aging global population. Aims: To determine cost-of-disease of heart failure (HF) in Turkey from the payer perspective. Study Design: Cross-sectional cost of disease study. Methods: In this cost-of-disease study, annual direct and indirect costs of management of HF were determined based on epidemiological, clinical and lost productivity inputs provided by a Delphi panel consisted of 11 experts in HF with respect to ejection fraction (EF) status (HF patients with reduced EF (HFrEF), mid-range EF (HFmrEF) and preserved EF (HFpEF)) and New York Heart Association (NYHA) classification. Direct medical costs included cost items on outpatient management, inpatient management, medications, and non-pharmaceutical treatments. Indirect cost was calculated based on the lost productivity due to absenteeism and presenteeism. Results: 51.4%, 19.5%, and 29.1% of the patients were estimated to be HFrEF, HFmrEF, and HFpEF patients, respectively. The total annual direct medical cost per patient was $887 and non-pharmaceutical treatments ($373, 42.1%) were the major direct cost driver. Since an estimated nationwide number of HF patients is 1,128,000 in 2021, the total annual national economic burden of HF is estimated to be $1 billion in 2021. The direct medical cost was higher in patients with HFrEF than in those with HFmrEF or HFpEF ($1,147 vs. $555 and $649, respectively). Average indirect cost per patient was calculated to be $3,386 and was similar across HFrEF, HFmrEF and HFpEF groups, but increased with advanced NYHA stage. Conclusion: Our findings confirm the substantial economic burden of HF in terms of both direct and indirect costs and indicate that the non-pharmaceutical cost is the major direct medical cost driver in HF management, regardless of the EF status of HF patients.

Pre-Discharge and Post-Discharge Management and Treatment Optimization in Acute Heart Failure.

Acute heart failure is associated with high mortality and rehospitalization rates and required urgent evaluation and early initiation or intensification of therapy. The risk of death and heart failure rehospitalization is greatest in the early post-discharge period, particularly within the first 3-6 months, and declines over time, which is referred as a vulnerable period of acute heart failure hospitalization. Therefore, implementation of guidelines-directed optimal therapy is not only so crucial in the acute phase but also very important in the pre-discharge and early post- discharge period in reducing mortality and rehospitalization rates. The pre-discharge period represents a window of opportunity for treatment optimization which includes to eliminate congestion, to treat comorbidities or precipitating factors, and to initiate or uptitrate oral ther- apy before discharge. Early assessment in the post-discharge period based on clinical evalu- ation and laboratory exams, further optimization of disease-modifying therapy is associated with lower 30-day hospitalization for heart failure. In clinical practice, clinicians usually focus on acute phase intravenous medications and short-term device therapies and, in fact, neglect short- and long-term comprehensive approaches. This paper reviews management strategies that may help reduce mortality and heart failure rehospitalizations in pre-discharge and post- discharge periods and include adopting holistic approaches for heart failure, increasing optimi- zation of evidence-based therapies, treating cardiac and noncardiac comorbidities, improving care transitions, monitoring, and disease management.