Effect of sodium-glucose co-transporter-2 inhibitor empagliflozin on disease progression in a patient with heart failure and preserved ejection fraction.

Sodiumglucose co-transporter 2 inhibitors - gliflozins - have a scientific evidence on efficacy in patients with heart failure regardless left ventricular ejection fraction. Gliflozins They reduced combined endpoint of cardiovascular mortality and heart failure hospitalization also in patients with heart failure and left ventricular ejection fraction above 40 %. We report a case study of a patient with new onset heart failure. Early initiation of therapy with empagliflozin was associated with an improvement of symptoms and laboratory parameters including NT-proBNP level.

Role of eplerenone in the threatment of cardiovascular diseases.

Eplerenone is a selective mineralocorticoid receptor antagonist. Its approved for the therapy of patients with chronic heart failure with left ventricular systolic dysfunction and for the patients after myocardial infarction complicated by heart failure and left ventricular dysfunction. It´s also recommended for the therapy of primary hyperaldosteronism and the treatment of drug resistant hypertension.

Traditional and new biomarkers of congestion in heart failure.

The presence of pulmonary and systemic congestion is the main cause of the poor outcome of the patients with heart failure. Despite of the availability of several tools of the modern medicine, the degree of congestion is usualy difficult to evaulate. The clinical, imaging and laboratory methods are the tools, which can estimated the degree of congestion.

Effect of SGLT2 inhibitor empagliflozin on the stabilization of heart failure progress with the possibility of further interventions in a patient with HFrEF - a case report.

SGLT2 inhibitors are included in the first line medical therapy of HFrEF. We report a case study of a patient in whom introduction of treatment with empagliflozin after recurrent heart failure decompensation lead to stabilization of the progress of the disease. Heart failure progress stabilization enabled interventions of cardiovascular comorbidities with delay of heart transplantation or mechanical assist device implantation need.

Relation between Mid-Regional Pro-Adrenomedullin in Patients with Chronic Heart Failure and the Dose of Diuretics in 2-Year Follow-Up-Data from FAR NHL Registry.

Background and Objectives: The aim of this paper is to evaluate the impact of humoral substance mid-regional pro-adrenomedullin (MR-proADM) on the two-year survival of patients with chronic heart failure and relate it to the dosage of furosemide. Materials and Methods: The data is taken from the stable systolic heart failure (EF < 50%) FAR NHL registry (FARmacology and NeuroHumoraL activation). The primary endpoint at two-year follow-up was death, heart transplantation, or LVAD implantation. Results: A total of 1088 patients were enrolled in the FAR NHL registry; MR-proADM levels were available for 569 of them. The mean age was 65 years, and 81% were male. The aetiology of HF was ischemic heart disease in 53% and dilated cardiomyopathy in 41% of patients. The mean EF was 31 ± 9%. Statistically significant differences (p < 0.001) were obtained in several parameters: patients with higher MR-proADM levels were older, rated higher in NYHA class, suffered more often from lower limb oedema, and had more comorbidities such as hypertension, atrial fibrillation, diabetes, and renal impairment. MR-proADM level was related to furosemide dose. Patients taking higher doses of diuretics had higher MR-proADM levels. The mean MR-proADM level without furosemide (n = 122) was 0.62 (±0.55) nmol/L, with low dose (n = 113) 1−39 mg/day was 0.67 (±0.30) nmol/L, with mid dose (n = 202) 40−79 mg/day was 0.72 (±0.34) nmol/L, with high dose (n = 58) 80−119 mg/day was 0.85 (±0.40) nmol/L, and with maximum dose (n = 74) ≥120 mg/day was 1.07 (±0.76) nmol/L, p < 0.001. Patients with higher MR-proADM levels were more likely to achieve the primary endpoint at a two-year follow-up (p < 0.001) according to multivariant analysis. Conclusions: Elevated plasma MR-proADM levels in patients with chronic heart failure are associated with an increased risk of death and hospitalization. Higher MR-proADM levels in combination with increased use of loop diuretics reflect residual congestion and are associated with a higher risk of severe disease progression.

Long-term follow-up of a patient undergoing interatrial shunt device implantation for treatment of heart failure with a preserved ejection fraction.

We herein present a case study of a patient with heart failure with a preserved ejection fraction and severe symptoms who underwent interatrial shunt device implantation and follow-up at a tertiary care heart failure clinic. The interatrial shunt device implantation was successful. No adverse events occurred, and the device prevented hospitalization for heart failure during long-term follow-up.

Acute effect of spinal cord stimulation on autonomic nervous system function in patients with heart failure.

AIMS: To test the hypothesis that spinal cord stimulation (SCS) acutely improves heart rate variability (HRV) and baroreceptor sensitivity (BRS) in patients with heart failure (HF). METHODS: SCS (15 minutes) was delivered in four different settings: 90% of maximal tolerated stimulation amplitude (MTA) targeting the T1-T4 spinal cord segments (SCS90T1-4), 60% of MTA (SCS60T1-4), 90% of MTA with cranial (SCS90CR) and caudal (SCS90CA) electrode configuration. HRV and BRS were recorded continuously and stimulation was compared to device off. RESULTS: Fifteen HF patients were included. SCS90T1-4 did not change the standard deviation of intervals between normal beats (SDNN, p = 0.90), BRS (p = 0.55) or other HRV parameters. In patients with baseline SDNN <50 ms, SCS90T1-4 significantly increased SDNN (p = 0.004). CONCLUSIONS: Acute SCS at 60-90% of MTA targeting upper thoracic spinal cord segments does not improve autonomic balance or baroreceptor sensitivity in unselected patients with heart failure but may improve HRV in patients with low SDNN.

Trends in the treatment and survival of heart failure patients: a nationwide population-based study in the Czech Republic.

AIMS: A retrospective nationwide observational analysis of diagnoses, procedures, and treatment reported to the Czech National Registry of Reimbursed Health Services between 2012 and 2018. METHODS AND RESULTS: Prevalence of heart failure (HF) patients increased from 176 496 (1679.4 per 100 000 population) in 2012 to 285 745 (2689.0 per 100 000 population) patients in 2018 (mean age 74.4 ± 12.8 years). In the last years, a stable incidence of HF patients was observed (544 per 100 000 population in 2016 vs. 551 per 100 000 population in 2018; P = 0.310). Mortality rate decreased from 20.55% in 2012 to 15.89% in 2018. The number of hospitalized patients remained similar (318.2 per 100 000 population in 2012 vs. 311.8 per 100 000 population in 2018; P = 0.479). The most used drugs were diuretics (173 295; 60.6%) and beta-blockers (178 823; 62.6%), followed by angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (angiotensin-converting enzyme inhibitors 120.581; 42.2%; angiotensin II receptor blockers 47 216; 16.5%). Even though the whole number of implanted devices in HF patients increased steadily (from 25 205 in 2012 to 45 363 in 2018), the prevalence of all devices (pacemakers and defibrillators) in the HF patients remained about the same (14.3% in 2012; 15.9% in 2018). CONCLUSIONS: The study included all patients with HF in the Czech Republic. These are the first nationwide data of HF epidemiology in the Eastern bloc. The incidence of HF remains stable in the last years. Due to aging of the population, the prevalence of HF significantly increased in the last 6 years. Despite a continuous increase in the prevalence of HF and a suboptimal utilization of its pharmacological therapy, mortality decreased, and the number of hospitalized patients remained the same.

Pacemaker-Based Cardiac Neuromodulation Therapy in Patients With Hypertension: A Pilot Study.

Background In prior unblinded studies, cardiac neuromodulation therapy (CNT) employing a sequence of variably timed short and longer atrioventricular intervals yielded sustained reductions of systolic blood pressure (SBP) in patients with hypertension. The effects of CNT on SBP were investigated in this double-blind randomized pilot study. Methods and Results Eligible patients had daytime ambulatory SBP (aSBP) ≥130 mm Hg and office SBP ≥140 mm Hg despite taking ≥1 antihypertensive medication, and an indication for a dual-chamber pacemaker. Patients underwent Moderato device implantation, which was programmed as a standard pacemaker during a 1-month run-in phase. Patients whose daytime aSBP was ≥125 mm Hg at the end of this period were randomized (1:1, double blind) to treatment (CNT) or control (CNT inactive). The primary efficacy end point was the between-group difference of the change in 24-hour aSBP at 6 months. Of 68 patients initially enrolled and who underwent implantation with the Moderato system, 47 met criteria for study continuation and were randomized (26 treatment, 21 control). The mean age was 74.0±8.7 years, 64% were men, left ventricular ejection fraction was 59.2%±5.7%, and aSBP averaged 141.0±10.8 mm Hg despite the use of 3.3±1.5 antihypertensive medications; 81% had isolated systolic hypertension. Six months after randomization, aSBP was 11.1±10.5 mm Hg (95% CI, -15.2 to -8.1 mm Hg) lower than prerandomization in the treatment group compared with 3.1±9.5 mm Hg (-7.4 to 1.2 mm Hg) lower in controls, yielding a net treatment effect of 8.1±10.1 mm Hg (-14.2 to -1.9 mm Hg) (P=0.012). There were no Moderato device- or CNT-related adverse events. Conclusions CNT significantly reduced 24-hour aSBP in patients with hypertension with a clinical indication for a pacemaker. The majority of patients had isolated systolic hypertension, a particularly difficult group of patients to treat. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02837445.

Prognostic value of high-sensitivity cardiac troponin I in heart failure patients with mid-range and reduced ejection fraction.

BACKGROUND: The identification of high-risk heart failure (HF) patients makes it possible to intensify their treatment. Our aim was to determine the prognostic value of a newly developed, high-sensitivity troponin I assay (Atellica®, Siemens Healthcare Diagnostics) for patients with HF with reduced ejection fraction (HFrEF; LVEF < 40%) and HF with mid-range EF (HFmrEF) (LVEF 40%-49%). METHODS AND RESULTS: A total of 520 patients with HFrEF and HFmrEF were enrolled in this study. Two-year all-cause mortality, heart transplantation, and/or left ventricular assist device implantation were defined as the primary endpoints (EP). A logistic regression analysis was used for the identification of predictors and development of multivariable models. The EP occurred in 14% of the patients, and these patients had higher NT-proBNP (1,950 vs. 518 ng/l; p < 0.001) and hs-cTnI (34 vs. 17 ng/l, p < 0.001) levels. C-statistics demonstrated that the optimal cut-off value for the hs-cTnI level was 17 ng/l (AUC 0.658, p < 0.001). Described by the AUC, the discriminatory power of the multivariable model (NYHA > II, NT-proBNP, hs-cTnI and urea) was 0.823 (p < 0.001). Including heart failure hospitalization as the component of the combined secondary endpoint leads to a diminished predictive power of increased hs-cTnI. CONCLUSION: hs-cTnI levels ≥ 17 ng/l represent an independent increased risk of an adverse prognosis for patients with HFrEF and HFmrEF. Determining a patient's hs-cTnI level adds prognostic value to NT-proBNP and clinical parameters.

Long-Term Results of Hybrid Left Ventricular Reconstruction in the Treatment of Ischemic Cardiomyopathy.

The evidence supporting surgical aneurysmectomy in ischemic heart failure is inconsistent. The aim of the study was to describe long-term effect of minimally invasive hybrid transcatheter and minithoracotomy left ventricular (LV) reconstruction in patients with ischemic cardiomyopathy. Twenty-three subjects with transmural anterior wall scarring, LV ejection fraction 15-45%, and New York Heart Association class ≥ II were intervened using Revivent TC anchoring system. LV end-systolic volume index was reduced from 73.2 ± 27 ml at baseline to 51.5 ± 22 ml after 6 months (p < 0.001), 49.9 ± 20 ml after 2 years (p < 0.001), and 56.1 ± 16 ml after 5 years (p = 0.047). NYHA class improved significantly at 5 years compared to baseline. Six-min walk test distance increased at 2 years compared to the 6-month visit. Hybrid LV reconstruction using the anchoring system provides significant and durable LV volume reduction during 5-year follow-up in preselected patients with ischemic heart failure. Legend: Hybrid left ventricular reconstruction using the anchoring system provides significant and durable LV volume reduction throughout 5-year follow-up in preselected patients with ischemic heart failure.

Surgical ablation of the right greater splanchnic nerve for the treatment of heart failure with preserved ejection fraction: first-in-human clinical trial.

AIMS: Inappropriate control of blood volume redistribution may be a mechanism responsible for exercise intolerance in heart failure with preserved ejection fraction (HFpEF). We propose to address this underlying pathophysiology with selective blockade of sympathetic signalling to the splanchnic circulation by surgical ablation of the right greater splanchnic nerve (GSN). METHODS AND RESULTS: In a single-arm, prospective, two-centre trial, 10 patients with HFpEF (50% male, mean age 70 ± 3 years) all with New York Heart Association (NYHA) class III, left ventricular ejection fraction >40%, pulmonary capillary wedge pressure (PCWP) ≥15 mmHg at rest or ≥25 mmHg with supine cycle ergometry, underwent ablation of the right GSN via thoracoscopic surgery. Patients were evaluated at baseline, 1, 3, 6 and 12 months after the procedure. The primary endpoint was a reduction in exercise PCWP at 3 months. There were no adverse events related to the blockade of the nerve during 12-month follow-up but three patients had significant peri-procedural adverse events related to the surgical procedure itself. At 3 months post-GSN ablation, patients demonstrated a reduction in 20 W exercise PCWP when compared to baseline [-4.5 mmHg (95% confidence interval, CI -14 to -2); P = 0.0059], which carried over to peak exercise [-5 mmHg (95% CI -11 to 0; P = 0.016). At 12 months, improvements were seen in NYHA class [3 (3) vs. 2 (1, 2); P = 0.0039] and quality of life assessed with the Minnesota Living with Heart Failure Questionnaire [60 (51, 71) vs. 22 (16, 27); P = 0.0039]. CONCLUSION: In this first-in-human study, GSN ablation in HFpEF proved to be feasible, with a suggestion of reduced cardiac filling pressure during exercise, improved quality of life and exercise capacity.

Expert consensus on the practical aspects of the cooperation of cardiologist and diabetologist in the management of the patients with chronic heart failure and reduced ejection fraction.

Diabetes mellitus is an important risk factor for the development of heart failure and presence of diabetes significantly worsens heart failure outcome. Introduction of gliflozins to the therapy of heart failure is one of the most important novelty. Gliflozins reduce glucose level by the sodium-glucose contransporter 2 inhibition in proximal tubulus in the kidney. Gliflozins are used as effective antidiabetic drugs with improvement of glycemic control without risk of hypoglycemia, gliflozins decrease blood pressure and patients weight. Recent studies have shown that gliflozins significantly reduce risk of cardiovascular complications and heart failure hospitalizations in diabetic patients. Clinical trials with dapagliflozin and empagliflozin have shown reduction of the risk of cardiovascular death and heart failure hospitalization in the patients with heart failure and reduced ejection fraction both in the patients with diabetes and in the patients without diabetes. The aim of the expert consenzus is to summarize practical aspects in the cooperation of cardiologist and diabetologist in the management of the patients with heart failure and reduced ejection fraction in the context of the current guidelines and other treatment options.

Expert consensus on the importance of iron deficiency and the possibility of its correction in patients with heart failure.

Anemia and iron deficiency are common non-cardiovascular comorbidities of heart failure. The prevalence of iron deficiency is up to 55 % of patients with chronic heart failure and up to 80 % subjects with acute heart failure including acute decompensated heart failure, independently on anemia. The European Society of Cardiology Heart Failure Guidelines 2021 recommend intravenous iron replacement in patients with heart failure and iron deficiency to improve symptoms, stress tolerance and quality of life in chronic heart failure and to reduce risk of subsequent hospitalization after acute decompenstation.

Novel Neuromodulation Approach to Improve Left Ventricular Contractility in Heart Failure: A First-in-Human Proof-of-Concept Study.

BACKGROUND: Morbidity and mortality outcomes for patients admitted for acute decompensated heart failure are poor and have not significantly changed in decades. Current therapies are focused on symptom relief by addressing signs and symptoms of congestion. The objective of this study was to test a novel neuromodulation therapy of stimulation of epicardial cardiac nerves passing along the posterior surface of the right pulmonary artery. METHODS: Fifteen subjects admitted for defibrillator implantation and ejection fraction ≤35% on standard heart failure medications were enrolled. Through femoral arterial access, high fidelity pressure catheters were placed in the left ventricle and aortic root. After electro anatomic rendering of the pulmonary artery and branches, either a circular or basket electrophysiology catheter was placed in the right pulmonary artery to allow electrical intravascular stimulation at 20 Hz, 4 ms pulse width, and ≤20 mA. Changes in maximum positive dP/dt (dP/dtMax) indicated changes in ventricular contractility. RESULTS: Of 15 enrolled subjects, 5 were not studied due to equipment failure or abnormal pulmonary arterial anatomy. In the remaining subjects, dP/dtMax increased significantly by 22.6%. There was also a significant increase in maximum negative dP/dt (dP/dtMin), mean arterial pressure, systolic pressure, diastolic pressure, and left ventricular systolic pressure. There was no significant change in heart rate or left ventricular diastolic pressure. CONCLUSIONS: In this first-in-human study, we demonstrated that in humans with stable heart failure, left ventricular contractility could be accentuated without an increase in heart rate or left ventricular filling pressures. This benign increase in contractility may benefit patients admitted for acute decompensated heart failure.

Role of biomarkers of cardiac remodeling, myofibrosis, and inflammation in assessment of disease severity in euvolemic patients with chronic stable heart failure.

OBJECTIVE: This study aimed to determine the importance of biomarkers of chronic heart failure (CHF) for assessing disease severity in euvolemic stable patients. PATIENTS AND METHODS: N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor (GDF)-15, galectin-3, cystatin-C, soluble suppression of tumorigenicity 2 (sST2), tissue type inhibitor of matrix metalloproteinase (TIMP)-1, and ceruloplasmin levels were measured in euvolemic patients with stable CHF. Severity of CHF was defined by echocardiographic and biochemical parameters. RESULTS: In 160 patients (123 men and 37 women, mean age: 65.8±12.2 years), we found strong associations between NT-proBNP and bilirubin levels (r = 0.434) and the estimated glomerular filtration rate (r = -0.321). GDF-15 and cystatin-C levels were significantly correlated with parameters of kidney function. In multivariable regression analysis, NT-proBNP levels were associated with the left ventricular ejection fraction and left ventricular end-systolic volume (coefficient of determination R2 = 0.777). Additionally, GDF-15 levels were correlated with urea levels (R2 = 0.742), and cystatin C levels were correlated with urea and bilirubin levels (R2 = 0.732). CONCLUSION: Besides NT-proBNP, GDF-15 and cystatin C are promising biomarkers for establishing the severity of disease in euvolemic patients with stable CHF.

His bundle pacing after failure of cardiac resynchronization therapy: a case study.

His bundle pacing is a relatively new method of cardiac pacing. This method is used in patients with atrioventricular block to prevent heart failure associated with right ventricular pacing, and in patients with bundle branch block and cardiomyopathy. We report a patient with cardiomyopathy and left bundle branch block with failure of cardiac resynchronization therapy. Permanent His bundle pacing was associated with clinical improvement and improvement of parameters of cardiac function.

Heart rate as an independent predictor of long term mortality of acute heart failure patients in sinus rhythm according to their ejection fraction: data from the AHEAD registry.

BACKGROUND: Heart rate (HR) at admission in patients with acute heart failure (AHF) has been shown to be an important risk marker of in-hospital mortality. However, its relation with mid and long-term prognosis as well as the impact of Ejection Fraction (EF) is unknown. Our objective was to study the relationship between long-term survival and HR at admission depending on EF in a cohort of patients hospitalized for AHF. METHODS: We analyzed the data of 2335 patients in sinus rhythm hospitalized for AHF from AHEAD registry. Patients with cardiogenic shock and AHF from surgical or non-cardiac etiology were excluded. RESULTS: Survival rates at 6 and 12 months were 84.8% and 78% respectively. Increased age, decreased diastolic BP, lack of PCI during hospitalization, increased creatinine level and increased HR (with different cut-offs according to EF categories) were found as predictors whatever the EF at 6 and 12 months. Optimal prognostic cut-offs of heart rate were identified for Heart Failure with reduced EF at 100 bpm, for Heart Failure with mid-range EF at 90 bpm and for Heart Failure with preserved EF at 80 bpm for both 6 and 12 months. CONCLUSION: Our study suggests that HR at admission appears to be an independent prognostic parameter in AHF patients in sinus rhythm irrespective of EF and can be used to classify patients according to the severity of the disease.

Brachial pulse pressure in acute heart failure. Results of the Heart Failure Registry.

AIMS: To investigate the still uncertain independent prognostic impact of pulse pressure (PP) in acute heart failure (HF), in particular across the left ventricular ejection fraction (EF) phenotypes, and the potential contribution of PP in outlining the individual phenotypes. METHODS AND RESULTS: We prospectively evaluated 1-year death and rehospitalization in 4314 patients admitted for acute HF grouped by EF and stratified by their PP level on admission. In HF with reduced (< 40%) EF (HFrEF), the highest quartiles of PP had the lowest unadjusted [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.61-0.98] and adjusted (HR 0.64 0.50-0.82) risk of 1 year all cause death compared to the lowest quartile. Its prognostic impact was partially mediated by systolic blood pressure (SBP). In HF with preserved (≥ 50%) EF (HFpEF), the intermediate quartile of PP showed the lowest 1 year all cause mortality in unadjusted (HR 0.598, CI 0.416-0.858) and adjusted (HR 0.55, 95% CI 0.388-0.801) models with no relationship with SBP. In a receiver operating characteristic analysis, a combination of PP > 60 mmHg and SBP > 140 mmHg was associated to a preserved EF with a high performance value. No prognostic significance of PP was found in the HF with mid-range EF subgroup. CONCLUSIONS: In acute HFrEF, there is an almost linear inverse relation between mortality and PP, partly mediated by SBP. In HFpEF, a J-shaped relationship between mortality and PP was present with a better prognosis at the nadir. A combination of PP > 60 mmHg with SBP > 140 mmHg may be clinically helpful as marker of a preserved left ventricular EF.