Medical Treatment Of Heart Failure Research Articles

Obstructive sleep apnea and acute decompensated heart failure

Abstract Funding Acknowledgements None. Background Acute decompensated heart failure is a condition with a high frequency of hospitalizations and mortality. Screening and treatment for obstructive sleep apnea can be helpful in these patients. Purpose To determine the frequency of obstructive sleep apnea in patients with acute decompensated heart failure. To add CPAP home therapy to standard medical treatment for heart failure. To follow patients for 1 year. Methods We conducted a single-centre, prospective cohort study form 150 consecutive patients hospitalized for exacerbation heart failure in the cardiology department. 81 patients meet inclusion criteria – Apnea-Hypopnea index (AHI) > 5, Epworth Sleepiness Scale (ESS) > 8, NYHA class II/III and NTproBNP>900 pg/ml. Patients with OSA were offered to purchase a CPAP device for the home. They were divided into two groups with CPAP and no-CPAP. All patients receiving optimal medical treatment. The follow-up period was 1 year. At the end of the period, patients underwent a physical examination, an echocardiography, and ESS. In the non-CPAP group, 29 patients were followed up and 13 patients dropped out due to mortality. In the CPAP group, 16 patients were followed up, with 1 dropped out. Sleep apnea screening was performed with ApneaLinkTM. Echocardiographic assessment of left ventricular ejection fraction (LVEF) and the E/e‘m ratio. Results From 81 with sleep apnea 72.8% (n=59) has obstructive sleep apnea (OSA) and 27.2% (n=22) has central sleep apnea (CSA). Of the 59 patients with OSA, 17 patients (28.8%) purchased a device and continued therapy at home, while 42 patients (71.2%)on optimal drug therapy without CPAP. There is a statistically significant difference in BMI in the group with CPAP compared to the no-CPAP group at the beginning and at the end of the follow-up (CPAP group at the start 36.47±7.3 vs. the end 33.3±5.7, p=0.001 and no-CPAP group at the start 36.35±7.34 vs. the end 35.74±7.46 , p=0.356). A similar relationship is found in systolic blood pressure(SBP) and diastolic blood pressure(DBP). SBP in CPAP group at start 136.2±6.2 mmHg vs. end 123.1±5.9 mmHg; р<0.001. relative to no-CPAP group – start 131.2±9.8 mmHg vs. end 131.3±7.7 mmHg; р=0.965. DBP in CPAP group at start 85.9±6.7 mmHg vs. end 77.3±5.3 mmHg; р<0.001 and no-CPAP group start 82.1±7.4 mmHg vs. end 81.7±5.7 mmHg, р=0.644. There is a significant change in LVEF between the two groups at the beginning and at the end of the follow-up (in CPAP group at start 47.5±8.7, vs. at end 50.07±7.5; р=0.005, between no-CPAP at start 52.5±6.9 vs. at end 52.2±7.1; р=0.389). The CPAP group had a median survival of 11.7 months vs. 10.1 months in no CPAP group(Log Rank (Mental-Cox) p=0.044 ). Conclusion Obstructive sleep apnea is a common comorbidity in patients with acute decompensated heart failure. The addition of CPAP therapy in these patients improved BMI, SBP, DBP and increases LVEF. All this improves the prognosis for these patients.

Medical treatment of heart failure with renin–angiotensin–aldosterone system inhibitors and beta-blockers in aortic stenosis: association with long-term outcome after aortic valve replacement

Abstract Aims There is a lack of robust data on the optimal medical treatment of heart failure in patients with severe aortic stenosis, with no randomized controlled trials guiding treatment. The study aimed to study the association between exposure to renin–angiotensin–aldosterone system (RAS) inhibitors or beta-blockers and outcome after aortic valve replacement in patients with aortic stenosis and heart failure. Methods and results The study included all patients with heart failure undergoing aortic valve replacement for aortic stenosis in Sweden between 2008 and 2016 (n = 4668 patients). Exposure to treatment was assessed by a continuous tracking of drug dispensations, and outcome events were all-cause mortality and hospitalization for heart failure collected from national patient registries. After adjustment for age, sex, atrial fibrillation, hypertension, diabetes mellitus, and prior myocardial infarction, Cox regression analysis showed that RAS inhibition was associated with a lower risk of all-cause mortality in patients with reduced left ventricular ejection fraction (LV-EF) [hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.51–0.65] and preserved LV-EF (HR 0.69, 95% CI 0.56–0.85). Beta-blockade was associated with a lower risk of all-cause mortality in patients with reduced LV-EF (HR 0.81, 95% CI 0.71–0.92), but not in preserved LV-EF (HR 0.87, 95% CI 0.69–1.10). There was no association between RAS inhibition or beta-blockade and the risk of hospitalization for heart failure. Conclusion The RAS inhibition was associated with a lower all-cause mortality after valve replacement in patients with both reduced and preserved LV-EF. Beta-blockade was associated with lower all-cause mortality only in patients with reduced LV-EF.

Ponatinib-induced dilated cardiomyopathy: a case report

Ponatinib is a third-generation tyrosine kinase inhibitor with potent efficacy in the treatment of acute and chronic leukemia. Despite having an effective and sustained activity in all BCR-ABL1 mutations, it may cause cardiovascular adverse effects. Here we report a 56-year-old male patient with Chronic myeloid leukemia and no prior cardiac disorder who developed acute heart failure under ponatinib treatment. Guideline-recommended medical treatment for heart failure was initiated. Coronary angiography to exclude ischemic heart disease revealed no coronary stenosis. Cardiac magnetic resonance imaging showed findings consistent with non-ischemic dilated cardiomyopathy. After interruption of ponatinib treatment, cardiac evaluation showed improvement in left ventricular ejection fraction. Patients on Ponatinib therapy should be closely monitored for signs and symptoms of heart failure.

Effect of Sacubitril/Valsartan and enalapril on left ventricular function in patients with hematologic malignancies after bone marrow transplantation

Abstract Funding Acknowledgements Type of funding sources: None. Background and Aims Chemotherapy is known for its potential adverse effects on myocardium. Optimal medical treatment for heart failure may reverse myocardial dysfunction in the early stages of toxicity development. We hypothesized that early initiation of treatment with sacubitril/valsartan (s/v) or enalapril (ena) might prevent cardiotoxicity. Patients and methods 90 patients (mean age 45.7 ± 14,1 years old, 52 male) with preserved ejection fraction, who suffered from hematologic malignancies (lymphoma, leukemia) and underwent bone marrow transplantation, were randomized to receive sacubitril/valsartan 24/26 mg bid daily or enalapril 5 mg bid daily or placebo. We measured at baseline, before transplantation and after six months: i) Global Longitudinal Strain (GLS) of left ventricle (LV) by speckle tracking imaging, ii) myocardial global work index (GWI), global constructive work (GCW), global wasted work (GWW) and myocardial global work efficiency (GWE), by longitudinal strain-peripheral blood pressure loops, and iii) Left Ventricular Ejection Fraction (LVEF Simpson’s Method). Results The two treatment groups had similar age, sex atherosclerotic risk factors and cardiotoxic medication before and after bone marrow transplantation. Compared to baseline, patients treated with sacubitril/valsartan or enalapril for six months did not show a deterioration of LV GLS (−19.8±2.8 vs −19.3±4.1%, p = 0.403 for s/v, −20.3±2.8 vs −20.0±3.6%, p = 0.634 for ena). Conversely, patients treated with placebo for six months, presented a significant impairment of LV GLS (−20.9±2.1% vs −18.5±2.2, p = 0,001). No significant changes were found in LVEF after treatment with sacubitril/valsartan or enalapril for six months (57.5±4.9 vs 57.9±6.8%, p = 0.826 for s/v, 58.8±5.4 vs 60.7±7.1%, p = 0.419, for ena), while a borderline deterioration was noticed after treatment with placebo for six months (60.6±5.4 vs 57.7±6.7%, p = 0,045). We did not notice any alteration in GWi, GCW, GWW, GWE in patients treated with enalapril. On the other hand, in patients treated with sacubitril/valsartan GWE was improved (94.2±3.1 vs 95.8±1.8 %, p = 0.030) and GWW was diminished (111.5±75.7 vs 86.4±43.1 mmHg%, p = 0.045), while GWI and GCW did not show any significant alteration. Conversely, in the placebo group, GWI was reduced (1909.9±336.4 vs 1727.9±340.9 mmHg%, p = 0.027), GWW was increased (80.7±60.6 vs 110.6±65.1 mmHg%, p = 0.045), GWE was diminished (95.9±2.1 vs 94.1±3.9 %, p = 0.039) and GCW did not change. Conclusions Treatment with sacubitril/valsartan or enalapril prevented deterioration of myocardial function six months after bone marrow transplantation in patients with hematologic malignancies and preserved ejection fraction. Moreover, sacubitril/valsartan showed a more favorable effect on myocardial work.

Heart failure treatment in patients with and without obesity with an ejection fraction below 50.

The aim of this study was to assess heart failure (HF) treatment in patients with and without obesity in a large contemporary real-world Western European cohort. Patients with a left ventricular ejection fraction (LVEF) <50% and available information on body mass index (BMI) were selected from the CHECK-HF registry. The CHECK-HF registry included chronic HF patients in the period between 2013 and 2016 in 34 Dutch outpatient clinics. Patients were divided into BMI categories. Differences in HF medical treatment were analysed, and multivariable logistic regression analysis (dichotomized as BMI <30 kg/m2 and ≥30 kg/m2 ) was performed. Seven thousand six hundred seventy-one patients were included, 1284 (16.7%) had a BMI ≥30 kg/m2 , and 618 (8.1%) had a BMI ≥35 kg/m2 . Median BMI was 26.4kg/m2 . Patients with obesity were younger and had a higher rate of comorbidities such as diabetes mellitus, hypertension and obstructive sleep apnoea (OSAS). Prescription rates of guideline-directed medical therapy (GDMT) increased significantly with BMI. The differences were most pronounced for mineralocorticoid receptor antagonists (MRAs) and diuretics. Patients with obesity more often received the guideline-recommended target dose. In multivariable logistic regression, obesity was significantly associated with a higher likelihood of receiving ≥100% of the guideline-recommended target dose of beta-blockers (OR 1.34, 95% CI 1.10-1.62), renin-angiotensin system (RAS)-inhibitors (OR 1.34, 95% CI 1.15-1.57) and MRAs (OR 1.40, 95% CI 1.04-1.87). Guideline-recommended HF drugs are more frequently prescribed and at a higher dose in patients with obesity as compared to HF patients without obesity.

505 A NEW NEXN GENE VARIANT LEADING TO FOETAL ONSET MIXED PHENOTYPE CARDIOMYOPATHY WITH UNKNOWN PROGNOSIS

Abstract Background Idiopathic dilated cardiomyopathy (DCM) is a common cardiac disease phenotype known to result from many different triggers. Among possible etiologies, genetically determined forms have been more and more acknowledged: recent investigations made possible the identification of risk alleles and disease-causing variants encoding for structural components of the cardiac muscle. The NEXN gene encodes the protein nexilin, an essential protein for Z-disk stability. Homozygous NEXN variants are rare and associated with poor prognosis: fetal and perinatal death or severe DCM in infants. Case description we present the case of a male infant, born at term, with prenatal diagnosis of cardiomyopathy. Postnatally, DCM with severely reduced systolic function was confirmed (LVEDd 19 mm, +2 z-scores; LVEF 25%), along with biventricular hypertrophy. The infant required medical treatment for heart failure; atrial tachyarrhythmia responsive to amiodarone was associated. Family history oriented for a genetic and familiar form of DCM (consanguinity and sudden death at a young age on both sides). Whole Exome Sequencing revealed in the proband the homozygous variant c.1156dup (p.Met386fs) in the NEXN gene (NM_144573.4), and both parents were confirmed to be carrier of the same variant at the heterozygous state. This NEXN variant has not been described previously. Complete cardiac evaluation was performed in first-degree relatives, including echocardiography and Cardiac Magnetic Resonance; the mother shows early signs of CMP, such as LBBB with mildly reduced LVEF (53%), while the only remarkable finding for the father is mild left ventricular hypertrophy. Discussion genetic DCM can have different clinical courses. It is important to reach the diagnosis: family history is essential in raising suspicion, while infectious causes and inborn error of metabolism must be ruled out. Only a few cases of NEXN-related CMP are described in literature; surprisingly, and unlike what was previously described, we observed in our patient a favorable clinical course during time, suggesting a different severity compared to so far known NEXN variants. Conclusion This case helps to broaden present knowledge about NEXN variants and their clinical expression in humans, supporting the inclusion of the NEXN gene in the investigation of patients with DCM, in order to understand phenotypes, guide therapy, and provide proper genetic advice.

The impact of sacubitril/valsartan on outcome in patients suffering from heart failure with a concomitant diabetes mellitus.

Guidelines classify sacubitril/valsartan as a significant part of medical treatment of heart failure with reduced ejection fraction (HFrEF). Data have shown that the HbA1c levels in patients with diabetes mellitus could be impacted by sacubitril/valsartan. A possible positive effect in diabetes patients treated with sacubitril/valsartan on outcome and echocardiography parameters is not well studied yet. The aim of the present study was to compare the impact of sacubitril/valsartan on life-threatening arrhythmias, atrial fibrillation, different echocardiography parameters and congestion rate in patients suffering from HFrEF according to the diagnosis diabetes mellitus or no diabetes mellitus. Consecutive 240 patients with HFrEF from 2016 to 2020 were treated with sacubitril/valsartan and separated to concomitant diabetes mellitus (n=87, median age 68years interquartile range (IQR) [32-87]) or no diabetes mellitus (n=153, median age 66year IQR [34-89]). Different comorbidities and outcome data were evaluated over a follow-up period of 24months. Arterial hypertension (87% vs. 64%; P<0.01) and coronary artery disease (74% vs. 60%; P=0.03) were more often documented in patients with diabetes mellitus compared with patients without diabetes mellitus. Over the follow-up of 24months several changes were noted in both subgroups: Median left ventricular ejection fraction (EF) increased significantly in non-diabetes (27% IQR [3-44] at baseline to 35% IQR [13-64]; P<0.001), but not in diabetic patients (29% IQR [10-65] at baseline to 30% IQR [13-55]; P=0.11). Accordingly, NT-proBNP and troponin-I levels decreased significantly in non-diabetes patients (NT-brain natriuretic peptide [NT-proBNP] from median 1445pg/mL IQR [12.6-74676] to 491pg/mL IQR [13-4571]; P<0.001, troponin-I levels from 0.099ng/mL IQR [0.009-138.69] to 0.023ng/mL IQR [0.006-0.635]; P<0.001), but not in diabetic patients (NT-proBNP from 1395pg/mL IQR [100-29924] to 885pg/mL IQR [159-4331]; P=0.06, troponin-I levels from 0.05ng/mL IQR [0.013-103.0] to 0.020ng/mL IQR [0.015-0.514]; P=0.27). No significant change of laboratory parameters e. g. glomerular filtration rate, potassium level and creatinine levels were found in diabetes or non-diabetes patients. Comparing further echocardiography data, left atrial surface area, right atrial surface area, E/A ratio did not show a significant change either in the diabetes or non-diabetes group. However, the tricuspid annular plane systolic excursion was significantly increased in non-diabetes mellitus patients (from 17mm IQR [3-31] to 18mm [2.5-31]; P=0.04), and not in diabetic s patients (17.5mm IQR [8-30] to 18mm IQR [14-31]; P=0.70); the systolic pulmonary artery pressure remained unchanged in both groups. During follow-up, a similar rate of ventricular tachyarrhythmias was observed in both groups. The congestion rate decreased significantly in both groups, in diabetes patients (44.4% before sacubitril/valsartan and 13.5% after 24months treatment; P=0.0009) and in non-diabetic patients (28.4% before sacubitril/valsartan and 8.4% after 24months treatment; P=0.0004). The all-cause mortality rate was higher in patients with diabetes mellitus as compared with those without diabetes (25% vs. 8.1%; P<0.01). Sacubitril/valsartan reverses cardiac remodelling in non-diabetes patients. However, it reduces the congestion rate in diabetes and non-diabetes patients. The rates of ventricular tachyarrhythmias were similar in DM compared with non-DM over follow-up. The mortality rate remained to be over follow-up higher in diabetes patients compared with non-diabetes; however, it was lower compared with published data on diabetes and concomitant HFrEF not treated with sacubitril/valsartan.

Medical Treatment of Heart Failure with Reduced Ejection Fraction in the Elderly.

The aging population, higher burden of predisposing conditions and comorbidities along with improvements in therapy all contribute to the growing prevalence of heart failure (HF). Although the majority of trials have not demonstrated age-dependent heterogeneity in the efficacy or safety of medical treatment for HF, the latest trials demonstrate that older participants are less likely to receive established drug therapies for HF with reduced ejection fraction. There remains reluctance in real-world clinical practice to prescribe and up-titrate these medications in older people, possibly because of (mis)understanding about lower tolerance and greater propensity for developing adverse drug reactions. This is compounded by difficulties in the management of multiple medications, patient preferences and other non-medical considerations. Future research should provide a more granular analysis on how to approach medical and device therapies in elderly patients, with consideration of biological differences, difficulties in care delivery and issues relevant to patients’ values and perspectives. A variety of approaches are needed, with the central principle being to ‘add years to life – and life to years’. These include broader representation of elderly HF patients in clinical trials, improved education of healthcare professionals, wider provision of specialised centres for multidisciplinary HF management and stronger implementation of HF medical treatment in vulnerable patient groups.

Effect of Sacubitril/Valsartan or enalapril on left ventricular longitudinal strain in patients with hematologic malignancies after bone marrow transplantation

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Hellenic Association of Lipidiology, Atherosclerosis and Vascular disease Background and Aims Chemotherapy is known for its potential adverse effects on myocardium. Optimal medical treatment for heart failure may reverse myocardial dysfunction in the early stages of toxicity development. We hypothesized that early initiation of treatment with enalapril or sacubitril/valsartan could prevent cardiotoxicity. Patients and methods 60 patients (mean age 44,8± 14,1 years old, 34 male) with preserved ejection fraction, who suffered from hematologic malignancies (lymphoma, leukemia) and underwent bone marrow transplantation, were randomized to receive sacubitril/valsartan 24/26 mg bid daily or enalapril 5 mg bid daily or placebo. We measured at baseline, before transplantation, after three and after six months: i) Global Longitudinal Strain of left ventricle (LV) (GLS), ii) Left Ventricular End Diastolic Volume, Left Ventricular End Systolic Volume and Left Ventricular Ejection Fraction (LVEF Simpson’s Method). Results The three treatment groups had similar age, sex, atherosclerotic risk factors and cardiotoxic medication before, and after bone marrow transplantation. Compared to baseline, patients treated with sacubitril/valsartan did not show a deterioration of LV GLS at three and six months follow up (GLS=-20.2 ± 3.1% vs -19.8 ± 3.1%, p = 0.551 vs -19.6 ± 3.2%, p = 0.452, respectively). Similarly, compared to baseline, patients treated with enalapril did not show a deterioration of LV GLS at three and six months follow up (GLS=-20.7 ± 3.0% vs -20.5 ± 2.8%, p = 0.772 vs -20.3 ± 3.2%, p = 0.730, respectively). Conversely, patients treated with placebo, presented a significant impairment of LV GLS, at three and six months follow up (GLS=-20,5 ± 1.9% vs -18.5 ± 2.4%, p = 0.003 vs -18.6 ± 2.9%, p = 0.018, respectively). No significant changes were found in LVEF after treatment with sacubitril/valsartan (57,9 ± 5,6% vs 57,6 ± 6,1%, p = 0,733) or enalapril (59.2 ± 6.3% vs 60.4 ± 7.7%, p = 0.464) vs placebo (60,1 ± 5,6% vs 57,8 ± 6,6%, p = 0,166) at six months follow up. Conclusions Treatment with sacubitril/valsartan or enalapril prevented deterioration of myocardial deformation six months after bone marrow transplantation in patients with hematologic malignancies and preserved ejection fraction.

Angiotensin Receptor Neprilysin Inhibitor [ARNI] and Its Implications Ejection Fraction Preserved Heart Failure: A Recent Review

This review article discusses the Angiotensin Receptor-Neprilysin Inhibitor which is remedy made up of two anti-hypertensive pharmaceuticals (sacubitril and valsartan). These medications may prolong life expectancy more than ACE inhibitors, which have been routinely used to treat heart failure. ARNi is now being used to treat individuals with heart failure those who have a low ejection fraction, which means their basic pumping chamber isn't working properly. Patients must be symptomatic despite receiving effective medical treatment for heart failure or be unable to tolerate a sufficient dose of ACE inhibitors to be eligible. Sacubitril and/or Valsartan are the debut members of a latest class of drugs described as angiotensin receptor neprilysin inhibitors to receive FDA approval (ARNI). The FDA has approved the medicine for the management of chronic heart failure sufferers with a lower ejection fraction and NYHA classifications II, III, or IV.&#x0D; Before commencing sacubitril and/or valsartan, patients must have to be able to accommodate ACEI or ARB. This intervention covers the instances, mode of action, approaches of administration, significant toxic reactions, risks and benefits, bioactivity, and surveilling of sacubitril &amp; valsartan so as to the practitioners can control patients under therapy in settings into which it implies as a part of the effective interprofessional.

Prospects of heart failure pharmacotherapy: the latest news about omecamtiv mecarbil

Over the past decades, an active scientific research has been continuing aimed on the search for medications that can increase myocardial contractility and improve the course of heart failure (HF). omecamtiv mecarbil, a drug from the group of cardiac myosin activators, heads the list of applicants for clinical use. By today, evidences have been collected for the ability of omecamtiv mecarbil to bind exclusively to the heads of cardiac myosin molecules without significantly affecting smooth or skeletal muscle myosin. omecamtiv mecarbil stabilizes pre‑step myosin conformation, enabling the greater number of its heads to participate in the working phase of systole.The article presents the results of several randomized clinical trials that studied the efficacy and safety of omecamtiv mecarbil in heart failure: ATOMIC‑AHF, COSMIC‑HF and GALACTIC‑HF. ATOMIC‑AHF showed a tendency to reduce the risk of developing supraventricular and ventricular arrhythmias in heart failure. COSMIC‑HF has proven the ability of omecamtiv mecarbil to improve the quality of life of patients with heart failure. GALACTIC‑HF may be a turning point in the medical treatment of heart failure. For the first time, clinical evidence of the ability of the selective cardiac myosin activator omecamtiv mecarbil to improve myocardial contractile function, reduce the severity of symptoms of heart failure and reduce the risk of cardiovascular death in patients with the reduced left ventricular injection friction was obtained. It is too early to draw final conclusions about the advisability of omecamtiv mecarbil administration for heart failure. The findings of new comparative randomized clinical trials, systemic reviews and meta‑analyses may possibly alter the standards of treatment of this pathology.

Effect of Sacubitril/Valsartan on left ventricular longitudinal strain in patients with hematologic malignancies after bone marrow transplantation

Abstract Background and aims Chemotherapy is known for its potential adverse effects on myocardium. Optimal medical treatment for heart failure may reverse myocardial dysfunction in the early stages of toxicity development. We hypothesized that early initiation of treatment with sacubitril valsartan could prevent cardiotoxicity. Patients and methods 40 patients (mean age 45,3±13,1 years old, 23 male) with preserved ejection fraction, who suffered from hematologic malignancies (lymphoma, leukemia) and underwent bone marrow transplantation and were randomized to receive sacubitril/valsartan 24/26 mg bid daily or placebo. We measured at baseline, before transplantation, and after three months: i) Global Longitudinal Strain of left ventricle (LV) (GLS), ii) Left Ventricular Epicardial Strain (GLSepi), iii) Left Ventricular Endocardial Strain GLSendo), by speckle tracking imagind iv) Left Ventricular End Diastolic Volume, Left Ventricular End Systolic Volume and Left Ventricular Ejection Fraction (LVEF-Simpson's Method). Results The two treatment groups had similar age, sex atherosclerotic risk factors and cardiotoxic medication before and after bone marrow transplantation. Compared to baseline, patients treated with sacubitril/valsartan did not show a deterioration of LV GLS and GLSepi [(GLS = −20,2±3,1% vs −19,8±3,1%, p=0,551), (GLSepi = −17,9±2,8% vs −17,8±3,1%, p=0,855), (GLSendo = −23,02±3,6% vs −22,6±3,5%, p=0,572)], Conversely, patients treated with placebo group, presented a significant impairment of LV GLS and GLSepi [(GLS = −20,5±1,9% vs 18,5±2,3%, p=0,006, GLSepi = −18,1±1,5% vs −16,1±2,1%, p=0,003), (GLSendo = −23,4±2,2% vs −21,4±2,6%, p=0,008)] six months after bone marrow transplantation. No significant changes were found in LVEF after treatment with sacubitril/valsartan (57,9±5,6% vs 57,6±6,1%, p=0,733) or the placebo (60,1±5,6% vs 57,8±6,6%, p=0,166). However, in the sacubitril valsartan group, we noticed a significant reduction of left ventricular end diastolic and end-systolic volume [(103,1±27,01 ml vs 89,2±21,1 ml, p=0,012), (44,65±15,83 ml vs 36.4±8.3 ml, p=0,003), respectively]. Conclusions Treatment with sacubitril/valsartan prevented deterioration of myocardial deformation three months after bone marrow transplantation in patients with hematologic malignancies and preserved ejection fraction. Funding Acknowledgement Type of funding sources: None.

Gender differences in patients with structural heart disease undergoing VT ablation

This study sought to examine gender differences in patients with structural heart disease (SHD) referred for ablation of ventricular tachycardia (VT). Female patients are often underrepresented in large studies. Significant differences in the clinical presentation, treatment, and prognosis of female patients have been described in previous studies. We investigated 88 female patients with SHD undergoing VT ablation (mean age 59 years, 56% nonischemic cardiomyopathy, mean left ventricular ejection fraction 35%, 82% in electrical storm). A case-control study with 88 male patients was performed and the results regarding clinical and procedural characteristics, acute and long-term results of the two groups were compared. The female patients had more arrhythmogenic substrate, as they more commonly presented with electrical storm (p = .016) and had a higher number of inducible VT morphologies during the procedure (p = .018). Moreover, the female patients were less likely to have an optimized heart failure medical treatment at baseline (p = .030) and required more time from the first manifestation of the VT to ablation referral (p = .034). Although fewer epicardial ablations were performed in female patients (p = .019), the two groups showed similar results regarding VT noninducibility as ablation endpoint (p = .844), major procedure-related complications (p = .719) and freedom from VT during follow-up (p = .268). Moreover, the overall mortality in the two groups was similar (p = .176). Advanced NYHA class was associated with worse transplant and assist-device-free survival in the female group. Female patients presenting for VT ablation had more arrhythmogenic substrate and were less likely to have an optimized heart failure medical treatment. Nevertheless, the procedural acute and long-term outcomes between the two genders were similar.

Medical Treatment of Heart Failure: Ignore the Ejection Fraction and Treat All?

The left ventricular ejection fraction (LVEF), the most widely used index of LV function, has an essential role in defining heart failure (HF) phenotypes and guiding treatment of chronic HF. 1 Maddox TM Januzzi JL Allen LA Breathett K Butler J Davis LL et al. 2021 Update to the 2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2021; 77: 772-810 Crossref PubMed Scopus (83) Google Scholar

Medical treatment of heart failure with reduced ejection fraction: the dawn of a new era of personalized treatment?

Recent trials have shown the efficacy of new drugs for the medical therapy of heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduced hospitalizations for heart failure (HF), HF events, and cardiovascular death in patients with HFrEF or hospitalized for HF. Iron repletion with ferric carboxymaltose (FCM) improved symptoms, functional capacity, and quality of life in chronic HFrEF patients, and decreased the risk of subsequent HF hospitalizations in subjects with acutely decompensated HF. New-generation potassium binders may allow initiation and up-titration of renin-angiotensin-aldosterone system inhibitors (RASis). Lastly, the guanylate cyclase stimulator vericiguat and the myosin activator omecamtiv mecarbil reduced the primary endpoint in two major controlled trials. These results open novel pathways for the treatment of HFrEF. This review discusses new opportunities of an individualized approach to HFrEF pharmacotherapy, where new compounds expand a spectrum of drugs that target primarily neuroendocrine activation. SGLT2i can be safely applied once daily at a fixed dose to the vast majority of patients with HFrEF, including those with moderate renal dysfunction and/or systolic blood pressure as low as 95-100 mmHg. Additional medications are suitable for more specific phenotypes, with ivabradine providing benefit in patients with sinus rhythm and heart rates ≥70 b.p.m., FCM in the presence of iron deficiency, and potassium-lowering agents to implement RASi when hyperkalaemia occurs. Vericiguat and omecamtiv mecarbil also have potential for tailored approaches towards the haemodynamic status. Thus, a new era is starting for a more personalized medical treatment of HFrEF.

Ebstein anomaly, left ventricular hypertrabeculation and ventricular septal defect associated with a myh7 mutation

Abstract Funding Acknowledgements Type of funding sources: None. Ebstein anomaly is an extremely rare anomaly of &amp;lt;1% among all congenital heart diseases. Pathologically, the septal and / or posterior leaflet of the tricuspid valve has abnormal locations towards the right ventricular apex. Ebstein anomaly is especially accompanied by atrial septal defect, patent ductus arteriosus, wolf parkinson white syndrome and pulmonary atresia. Defects located in the interventricular septum are called the ventricular septal defect (VSD). They can be single or multiple and congenital or acquired. Isolated VSDs are the most common congenital anomaly in childhood and constitute 20-30% of all congenital heart diseases. VSD can be a part of major congenital malformations ,such as, fallot tetralogy, transposition of the major arteries, double ventricular right ventricle. Left ventricular noncompaction (LVNC) is a relatively common genetic cardiomyopathy, characterized by prominent trabeculations with deep intertrabecular recesses in mainly the left ventricle. Although LVNC often occurs in an isolated entity, it may also be present in various types of congenital heart disease . A combination of Ebstein anomaly, hypertrabeculation and ventricular septal defect is a rare condition. Case Report A 49-year-old male patient presented to the emergency room with shortness of breath and swelling of the legs. The patient had diagnosed an Ebstein anomaly while the military examination in 1988. Already it ‘s known that he has gout disease and uses colchicine but no family history of any disease. On examination of the patient, bilateral ral in respiratory sounds and +++ / +++ pretibial edema in the lower extremity were detected. On his electrocardiogram, the sinus rhythm with first-degree atrioventricular block was observed. The findings on his echocardiographic examination are ejection fraction 30-35% with global left ventricular hypokinesia, Ebstein anomaly (Figure ), perimembranous type VSD, atrial septal aneurysm type 2 and left ventricular hypertrabeculation. His blood table was normal. Medical treatment of heart failure was started for the patient who was interneed to the service. After getting clinical relief, the patient was discharged under medical treatment. Genetic tests were studied while following up at the heart failure outpatient clinic. In the MYH7 gene, splice-acceptor-2 (PVS1) variation heterozygous was detected. This variant has not been seen in national data banks of genetics. Conclusion The MYH7 gene, localized on chromosome 14p12, is composed of 41 exons and encodes the b-myosin heavy chain, expressed in cardiac muscle. Mutations in the MYH7 gene have been identified in association with left ventricular hypertrabeculation and Ebstein anomaly. In conclusion, this is the first known report of Ebstein anomaly associated with the splice-acceptor-2 variation heterozygous of the MYH7 gene. Abstract Figure

Beneficial effect of angiotensin converter enzyme inhibitors on left ventricular deformation in patients with hematologic malignancies after bone marrow transplantation

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Hellenic society of lipidiology, atherosclerosis and cardiovascular disease Background/Introduction: Optimal medical treatment for heart failure may reverse myocardial dysfunction in the early stages of cardiotoxic treatment. Patients and methods 60 patients age 46,3 ± 12,9 years old, 19 male) with preserved ejection fraction, who suffered from hematologic malignancies (lymphoma, leukemia) and underwent bone marrow transplantation, were randomized to receive 2,5 mg enalapril bid daily or placebo. We measured at baseline, before transplantation, and after three months: i) Global Longitudinal Strain of left ventricle (LV) (GLS), ii) LV Epicardial Strain (GLSepi), iii) LV Endocardial Strain (GLSendo), by speckle tracking imaging, iv) LV End Diastolic ,End Systolic Volume and Ejection Fraction (LVEF). Results The two treatment groups had similar age, sex atherosclerotic risk factors and cardiotoxic medication before and after bone marrow transplantation. Compared to baseline, patients treated with enalapril did not show a deterioration of LV GLS and GLSepi [ p = 0,540 and p = 0,422)], Conversely, patients treated with placebo group, presented a significant impairment of LV GLS and GLSepi [p = 0,041 and p = 0,028)] three months after bone marrow transplantation. No significant changes were found in LVEF after treatment with enalapril ( p = 0,692) or the placebo ( p = 0,892). Table 1 Conclusions Treatment with enalapril prevented deterioration of myocardial deformation three months after bone marrow transplantation Table 1 group baseline 3 months follow-up p Longitudinal strain apical 4 chambers view placebo -20.56 ± 2.55 -19.46 ± 2.59 0.154 enalapril -20.41 ± 3.31 -19.70 ± 3.70 0.433 Longitudinal strain apical 2 chambers view placebo -20.5 ± 1.97 -16.11 ± 10.38 0.149 enalapril -20.30 ± 3.90 -20.00 ± 3.82 0.763 Longitudinal strain apical 3 chambers view placebo -19.55 ± 2.36 -18.55 ± 2.43 0.197 enalapril -20.01 ± 4.09 -19.26 ± 3.68 0.489 Global Longitudinal Strain placebo -20.19 ± 1.76 -18.96 ± 2.08 0.041 enalapril -20.24 ± 3.58 -19.66 ± 3.65 0.540 Average Global Epicardial Strain placebo -17.82 ± 1.45 -16.60 ± 1.68 0.028 enalapril -17.84 ± 3.09 -17.16 ± 3.20 0.422 Average Global Endocardial Strain placebo -23.03 ± 2.15 -21.96 ± 2.56 0.181 enalapril -23.07 ± 4.19 -23.60 ± 4.17 0.666 EF (Simpon’s method) placebo 59.46 ± 6.59 59.69 ± 6.79 0.892 enalapril 58.65 ± 7.63 59.45 ± 9.28 0.692 Left ventricular parameters during 3 months of follow-up.

Expect the Unexpected in the Medical Treatment of Heart Failure with Reduced Ejection Fraction: between Scientific Evidence and Clinical Wisdom.

Over the past three decades, pharmacological treatment of heart failure (HF) with reduced ejection fraction (HFrEF) has witnessed a significant progress with the introduction of multiple disease-modifying therapies with a proven benefit on morbidity, mortality and quality of life. Recently, several novel medications (sacubitril/valsartan, sodium-glucose contransporter-2 [SGLT2] inhibitors, vericiguat and omecamtiv mecarbil) have shown to provide further improvement in outcomes in patients already receiving standard therapy for HFrEF. Available evidence suggests that sacubitril/valsartan and SGLT2 inhibitors (dapagliflozin and empagliflozin) are beneficial and well-tolerated in the majority inpatients and could be the mainstay treatment of HFrEF. Another group of medications (vericiguat and omecamtiv mecarbil) has shown promising results in reducing the risk of the composite of HF hospitalisation or cardiovascular mortality in patients with the more severe or advanced HF requiring recent hospitalisation. Therefore, these medications may be considered for the treatment of select group of patients with HFrEF with persisting or worsening symptoms despite optimal treatment. In addition, advances in pharmacological management of comorbidities frequently seen in HFrEF patients (diabetes, iron deficiency/anaemia, hyperkalaemia) provide further opportunities to improve outcomes. Given the increasing complexity of evidence-based therapies for HFrEF, there is a growing need to provide a practical perspective to their use. The purpose of this review is to summarise scientific evidence on the efficacy and safety of new and emerging medical therapies in HFrEF, with a focus on the clinical perspective of their use.

Effect of enalapril on left ventricular longitudinal strain in patients with hematologic malignancies after bone marrow transplantation

Abstract Background and aims Chemotherapy is known for its potential adverse effects on myocardium. Optimal medical treatment for heart failure may reverse myocardial dysfunction in the early stages of toxicity development. We hypothesized that early initiation of treatment with Angiotensin Converter Enzyme inhibitor (ACE-i) enalapril could prevent cardiotoxicity. Patients and methods 60 patients (mean age 46,3±12,9 years old, 19 male) with preserved ejection fraction, who suffered from hematologic malignancies (lymphoma, leukemia) and underwent bone marrow transplantation and were randomized to receive 2,5 mg enalapril bid daily or placebo. We measured at baseline, before transplantation, and after three months: i) Global Longitudinal Strain of left ventricle (LV) (GLS), ii) Left Ventricular Epicardial Strain (GLSepi), iii) Left Ventricular Endocardial Strain GLSendo), by speckle tracking imagind iv) Left Ventricular End Diastolic Volume, Left Ventricular End Systolic Volume and Left Ventricular Ejection Fraction (LVEF-Simpson's Method). Results The two treatment groups had similar age, sex atherosclerotic risk factors and cardiotoxic medication befeor and after bone marroe transplantation. Compared to baseline, patients treated with enalapril did not show a deterioration of LV GLS and GLSepi [(GLS = −20.2±3.6% vs 19.7±3.7%, p=0.540), (GLSepi = −17.9±3.1% vs −17.2±3.2%, p=0.422)], Conversely, patients treated with placebo group, presented a significant impairment of LV GLS and GLSepi [(GLS = −20.2±1.8% vs 18.9±2.1%, p=0.041, GLSepi = −17.8±1.5% vs −16.6±1.7%, p=0.028)] three months after bone marrow transplantation. No significant changes were found in LVEF after treatment with enalapril (58.6±17.6% vs 59.4±9.2%, p=0.692) or the placebo (59.4±6.6% vs 59.7±6.8%, p=0.892). Conclusions Treatment with enalapril prevented deterioration of myocardial deformation three months after bone marrow transplantation in patients with hematologic malignancies and preserved ejection fraction. Funding Acknowledgement Type of funding source: None

Sacubitil/valsartan in systemic right ventricular failure

Abstract Background In patients with heart failure with low ejection fraction (EF) (≤35%) sacubitril/valsartan is proven to be beneficial. We aimed to assess the effects of sacubitril/valsartan in adult congenital heart disease patients with failing systemic right ventricle (sRV) in the setting of congenitally corrected transposition of the great arteries (TGA) or TGA after atrial switch. Purpose To evaluate the feasibility and effect of treatment with sacubitril/valsartan in patients with heart failure in the setting of a sRV on optimal medical heart failure treatment. Methods Data of patients with sRV failure (estimated RVEF ≤35%) treated with sacubitril/valsartan were analyzed. Patients were clinically evaluated at baseline and at six months after initiation of the highest tolerated dose. Results Fourteen patients completed six-month follow-up thus far, of which 6 female (42.8%) and 2 (14.3%) with congenitally corrected transposition of the great arteries (TGA). After 6 months, 9 patients (64.3%) were using the highest dose (97/103 mg twice daily) of sacubitril/valsartan. NT-proBNP was significantly lower after 3 months and after 6 months compared with baseline (64% of baseline, p=0.006 and 53% of baseline, p=0.001, respectively). The kidney function did not change significantly (creatinine at baseline 83.6±12.0 and at 6 months 88.5±13.87, p=0.141) and serum potassium remained within normal limits (4.28±0.36 and 4.49±0.30, p=0.007). There was no significant decrease in systolic blood pressure (p=0.960). The echocardiographic sRV fractional area change (FAC) improved (p=0.002) and Global Longitudinal Strain (GLS) showed a trend towards improvement (p=0.058). During the 6 months of treatment, the exercise capacity remained stable, there was no increase in diuretic use, no serious adverse events and no heart failure related admissions occurred. Conclusion Treatment of sRV heart failure patients with sacubitril/valsartan leads to a significant reduction in NT-proBNP and significant increase in FAC. All patients remained clinically stable and no heart failure related admissions or serious adverse events occurred. Changes after 6 months Funding Acknowledgement Type of funding source: None