The Impact of Midodrine on Guideline-Directed Medical Therapy in Patients Admitted With Systolic Heart Failure.

ABSTRACT: Midodrine is occasionally used off-label to treat hypotension associated with advanced heart failure (HF); however, its association with changes in prescription of guideline-directed medical therapy (GDMT) is unknown. We sought to evaluate the effect of midodrine on the GDMT prescription pattern and clinical outcomes of patients with decompensated systolic HF. We retrospectively identified 114 patients admitted to our hospital in 2020 with decompensated systolic HF who were prescribed midodrine on discharge and compared them with 358 patients with decompensated systolic HF who were not prescribed midodrine. At 6 months, the midodrine group had more initiation or up-titration of beta blockers, renin-angiotensin-aldosterone system inhibitors, and sodium-glucose cotransporter-2 inhibitors compared with the nonmidodrine group. Survival at 6 months was similar between the 2 groups, but the midodrine group had more frequent rehospitalization for HF. Our findings suggest that midodrine is associated with improved GDMT in patients with decompensated HF but may be associated with worse prognosis.

Bioimpedance based determination of cardiac index does not show enough trueness for point of care use in patients with systolic heart failure.

Cardiac output (CO) is a key parameter in diagnostics and therapy of heart failure (HF). The thermodilution method (TD) as gold standard for CO determination is an invasive procedure with corresponding risks. As an alternative, thoracic bioimpedance (TBI) has gained popularity for CO estimation as it is non-invasive. However, systolic heart failure (HF) itself might worsen its validity. The present study validated TBI against TD. In patients with and without systolic HF (LVEF ≤ 50% or > 50% and NT-pro-BNP < 125 pg/ml, respectively) right heart catheterization including TD was performed. TBI (Task Force Monitor©, CNSystems, Graz, Austria) was conducted semi-simultaneously. 14 patients with and 17 patients without systolic HF were prospectively enrolled in this study. In all participants, TBI was obtainable. Bland-Altman analysis indicated a mean bias of 0.3 L/min (limits of agreement ± 2.0 L/min, percentage error or PE 43.3%) for CO and a bias of -7.3 ml (limits of agreement ± 34 ml) for cardiac stroke volume (SV). PE was markedly higher in patients with compared to patients without systolic HF (54% vs. 35% for CO). Underlying systolic HF substantially decreases the validity of TBI for estimation of CO and SV. In patients with systolic HF, TBI clearly lacks diagnostic accuracy and cannot be recommended for point-of-care decision making. Depending on the definition of an acceptable PE, TBI may be considered sufficient when systolic HF is absent.Trial registration number: DRKS00018964 (German Clinical Trial Register, retrospectively registered).

Impact of signal-averaged electrocardiography findings on appropriate shocks in prophylactic implantable cardioverter defibrillator patients with nonischemic systolic heart failure.

BACKGROUND: Appropriate shock therapy is associated with subsequent all-cause death in heart failure (HF) patients who receive an implantable cardioverter defibrillator (ICD) for the primary prevention of sudden cardiac death. To evaluate the impact of signal-averaged electrocardiography (SAECG) findings on appropriate shocks in prophylactic ICD patients with nonischemic systolic HF. METHODS: We studied 86 patients with nonischemic HF and a left ventricular ejection fraction ≤ 35% who underwent new ICD implantation for the primary prevention of sudden cardiac death. We excluded patients who had a previously implanted permanent pacemaker and patients who received cardiac resynchronization therapy with an ICD. SAECG was performed before implantation. Abnormal SAECG findings were defined if 2 of the following 3 conditions were identified: filtered QRS duration (fQRS) ≥ 114 ms, root-mean-square voltage during the last 40 ms of the fQRS (RMS 40) < 20 µV, and duration of the low-amplitude potentials < 40 µV (LAS 40) > 38 ms; additionally, patients with a QRS complex ≥ 120 ms who met both the RMS 40 and LAS 40 criteria were also considered to have abnormal SAECG findings. The primary outcome was the first occurrence of appropriate shock after implantation of the ICD. The secondary outcomes were the first occurrence of inappropriate shock and all-cause mortality. RESULTS: Forty-two patients met the criteria for abnormal SAECG findings (49%). During a median follow-up period of 61 months, 17 patients (20%) died, 24 (28%) received appropriate shock therapy, and 19 (22%) received inappropriate shock therapy. There was a significantly higher incidence of appropriate shocks in patients with abnormal SAECG findings than in those with normal SAECG findings (log-rank test, p = 0.025). Multivariate analysis revealed that abnormal SAECG findings were independently associated with the occurrence of appropriate shock (hazard ratio 2.67, 95% confidential interval 1.14-6.26). However, abnormal SAECG findings were not related to inappropriate shock. There was no difference in the incidence of all-cause death between patients with abnormal and normal SAECG findings. CONCLUSIONS: Our results suggest that abnormal SAECG findings are associated with a high probability of appropriate shocks in prophylactic ICD patients with nonischemic systolic HF.

Retrospective Study of 573 Patients with Heart Failure Evaluated for Coronary Artery Disease at Toulouse University Center, France.

BACKGROUND Heart failure (HF) most commonly occurs due to ischemic heart disease from stenotic coronary artery disease (CAD). HF is classified into 3 groups based on the percentage of the ejection fraction (EF): reduced (HFrEF), mid-range (HFmrEF), and preserved (HFpEF). This retrospective study included 573 patients who presented with HF based on the evaluation of EF and were evaluated for CAD by coronary angiography before undergoing coronary angioplasty at a single center in Toulouse, France. MATERIAL AND METHODS This retrospective observational study included patients recently diagnosed with HF or acute decompensation of chronic HF and referred for coronary angiography at Toulouse University Hospital between January 2019 and May 2020. RESULTS Significant CAD was found in 55.8%, 55%, and 55% of the whole population, HFpEF, and HFrEF groups, respectively. Older age, male sex, and diabetes mellitus were the main risk factors for ischemic HF. Except for age and sex, patients with ischemic HFpEF were comparable to those with non-ischemic HFpEF, unlike the ischemic HFrEF group, which had more common cardiovascular risk factors than the non-ischemic HFrEF group. The ischemic HFpEF group had an older age and higher rate of dyslipidemia than the ischemic HFrEF group. CONCLUSIONS At our center, CAD was diagnosed in more than half of patients who presented with heart failure with preserved or reduced EF. Older age and male sex were the common risk factors in patients with HFpEF and HFrEF.

Diastolic and systolic left ventricular dysfunction and mortality in chronic kidney disease patients on haemodialysis.

AIMS: Left ventricular diastolic dysfunction (LVDD) and LV systolic dysfunction (LVSD) are prevalent in CKD, but their prognostic relevance is debatable. We intent to verify whether LVDD and LVSD are independently predictive of all-cause mortality and if they have comparable or different effects on outcomes. METHODS: A retrospective analysis was conducted of the echocardiographic data of 1285 haemodialysis patients followed up until death or transplantation. LVDD was classified into 4 grades of severity. Endpoint was all-cause mortality. RESULTS: During a follow-up of 30 months, 419/1285 (33%) patients died, 224 (53%) due to CV events. LVDD occurred in 75% of patients, grade 1 DD was the prevalent diastolic abnormality, and pseudonormal pattern was the predominant form of moderate-severe DD. Moderate-severe LVDD (HR 1.379, CI% 1.074-1.770) and LVSD (HR 1.814, CI% 1.265-2.576) independently predicted death; a graded, progressive association was found between LVDD categories and the risk of death; and the impact of isolated severe-moderate LVDD on the risk of death was comparable to that exercised by isolated compromised LV systolic function. CONCLUSION: Moderate-severe LVDD and LVSD were independently associated with a higher probability of death and had a similar impact on survival. A progressive association was observed between LVDD grades and mortality.

Effect of Canagliflozin Compared With Sitagliptin on Serum Lipids in Patients with Type 2 Diabetes Mellitus and Heart Failure with Reduced Ejection Fraction: A Post-Hoc Analysis of the CANA-HF Study.

ABSTRACT: The sodium glucose co-transporter 2 inhibitors have demonstrated favorable effects on cardiovascular and renal disease; however, they may also increase low-density lipoprotein cholesterol (LDL-C). There are limited data directly comparing the effects of sodium glucose co-transporter 2inhibitors on serum lipids to other antihyperglycemic therapies. In this post-hoc analysis of the CANA-HF trial, we sought to compare the effects of canagliflozin to sitagliptin in patients with type 2 diabetes mellitus (T2DM) and heart failure and reduced ejection fraction (HFrEF). The CANA-HF trial was a prospective, randomized controlled study that compared the effects of canagliflozin 100 mg daily to sitagliptin 100 mg daily on cardiorespiratory fitness in patients with HFrEF and T2DM. Of the 36 patients enrolled in CANA-HF, 35 patients had both baseline and 12-weeks serum lipids obtained via venipuncture. The change in LDL-C from baseline to 12 weeks was 5 (-12.5 to 19.5) mg/dL versus -8 (-19 to -1) mg/dL (P = 0.82) and triglyceride levels was -4 (-26 to 9) mg/dL and -10.5 (-50 to 29.3) mg/dL (P = 0.52) for canagliflozin and sitagliptin, respectively. No significant differences were found between canagliflozin and sitagliptin for total cholesterol, high-density lipoprotein cholesterol or non-HDL-C (P > 0.5 for all). These data suggest that compared with sitagliptin, canagliflozin may not increase LDL-C in patients with T2DM and HFrEF.

Safety and Efficacy of the Combination of Sacubitril/Valsartan and SGLT2i in HFrEF Patients (SECSI Registry).

ABSTRACT: Recent studies have proven benefit of SGLT2i drugs in patients with heart failure with reduced ejection fraction (HFrEF), but their safety when combined with angiotensin-neprilysin inhibitor (ARNI) has not been established. The Safety and Efficacy of the Combination of Sacubitril/Valsartan and SGLT2i in HFrEF Patients registry was conducted to address this issue. SECSI registry is a consecutive, observational, retrospective, multicentre study conducted in 3 Heart Failure Units in Spain. It included 144 HFrEF patients who were treated with ARNI and iSGLT2. Data were collected at baseline, month 2, and month 6. The primary endpoint was the estimated glomerular filtration rate (eGFR), after the initiation of ARNI and sodium-glucose cotransporter-2 inhibitors (SGLT2i). Secondary endpoints included potassium levels and functional class (New York Heart Association class). There were 3 prespecified subgroup analyses: Elderly patients (≥70 years), patients with chronic kidney disease (KDIGO classification G3), and the sequence of drug initiation. Mean age was 69.9 ± 10.1 years, and 110 (76.4%) were men. Left ventricular ejection fraction was 32 ± 7.8%, and most patients were symptomatic [123 (87.2%) New York Heart Association II/III/IV]. eGFR decreased at month 2 and this trend was maintained at month 6 [eGFR baseline 68.5 ± 17.3, month 2 62 ± 19.7 and month 6 64.7 ± 8.6 mL/min/1.73 m2 (P < 0.01 for both)]. In prespecified analysis, elder patients and those who simultaneously initiate both treatments showed the steeper decrease in eGFR. To conclude, co-administration of SGLT2i and ARNI in routine care in HFrEF patients produced a slight decrease in eGFR at 6 months of follow-up. This decrease was especially significant in elder patients and those who initiate both drugs simultaneously.

Impact of optimal heart rate on left ventricular reverse remodeling and functional improvement in patients with systolic heart failure.

Heart rate modulation therapy using ivabradine reduces mortality and morbidity in patients with systolic heart failure, whereas too reduced heart rate seems to worsen the clinical outcome. The optimal heart rate during heart rate modulation therapy remains unknown. Consecutive patients with left ventricular ejection fraction < 50% who received echocardiographic assessments and simultaneous heart rate measurements were retrospectively investigated. Theoretically ideal heart rate was calculated using a previously proposed formula: 93 - 0.13 × (deceleration time [msec]). Impacts of heart rate on the 1-year echocardiographic left ventricular reverse remodeling were compared among the three groups stratified by the heart rate status: optimal heart rate group (within 10 bpm of ideal heart rate), below-optimal heart rate group (< 10 bpm of ideal heart rate), and above-optimal heart rate group (> 10 bpm of ideal heart rate). A total of 75 patients (70 years old, 60 men) were included. There were no significant differences in the baseline characteristics among the three groups, except for the higher prevalence of tolvaptan use and higher plasma B-type natriuretic peptide level in the below-optimal heart rate group. Left ventricular end-diastolic diameter (from 55 to 54) and left ventricular ejection fraction (from 39 to 46) improved significantly only in the optimal heart rate group at 1-year follow-up (p < 0.05 for both). Optimal heart rate, which was calculated using a formula consisting of deceleration time, was associated with cardiac reverse remodeling in patients with systolic heart failure. Prospective study to investigate the implication of deceleration time-guided aggressive heart rate optimization is the next concern.

Increased Red Cell Volume Is a Relevant Contributing Factor to an Expanded Blood Volume in Compensated Systolic Chronic Heart Failure.

BACKGROUND: In patients with chronic heart failure (CHF), volume overload is usually described as an expansion of plasma volume. Additional red cell volume (RCV) expansion is less commonly recognized. So far, little is known about quantitative differences in blood volume status and its different components in patients with stable CHF compared to healthy controls. METHODS: This study aimed to quantify blood volume and its constituents, RCV and plasma volume, by using an abbreviated carbon monoxide rebreathing method with particular focus on its primary measure total hemoglobin mass in 47 patients (10 women) with systolic CHF and a left ventricular ejection fraction of 29.0 ± 9.4%. These were compared to an age-matched control group of 84 healthy subjects (44 women) using the same method. RESULTS: In both absolute and body-surface-area-corrected analysis, hemoglobin mass (446 ± 81 vs 353 ± 64 g/m2) as well as RCV (1293 ± 231 vs 1033 ± 176 mL/m2) were significantly increased in CHF. In addition, significant plasma volume expansion was observed in CHF (2069 ± 400 vs 1750 ± 231 mL/m2) and, in conjunction with RCV, constituted a significantly increased blood volume (3361 ± 574 vs 2783 ± 369 mL/m2). In 66% of patients with compensated CHF, RCV was excessive compared to 14% in the control group. CONCLUSIONS: An increased RCV is a relevant contributing factor to hypervolemia in stable CHF. This is associated with an increased oxygen-carrying capacity, so it may be regarded as a possible compensatory mechanism for a reduced ejection fraction.

Phase 1B, Randomized, Double-Blinded, Dose Escalation, Single-Center, Repeat Dose Safety and Pharmacodynamics Study of the Oral NLRP3 Inhibitor Dapansutrile in Subjects With NYHA II-III Systolic Heart Failure.

ABSTRACT: The NLRP3 inflammasome has been implicated in the development and progression of heart failure. The aim of this study was to determine the safety of an oral inhibitor of the NLRP3 inflammasome, dapansutrile (OLT1177), in patients with heart failure and reduced ejection fraction (HFrEF). This was a phase 1B, randomized, double-blind, dose escalation, single-center, repeat dose safety and pharmacodynamics study of dapansutrile in stable patients with HFrEF (New York Heart Association Class II-III). Subjects were randomized to treatment with dapansutrile for up to 14 days at a ratio of 4:1 into 1 of 3 sequential ascending dose cohorts (500, 1000, or 2000 mg) each including 10 patients. Subjects underwent clinical assessment, biomarker determination, transthoracic echocardiogram, and maximal cardiopulmonary exercise testing at baseline, day 14, and day 28 to ascertain changes in clinical status. Placebo cases (N = 2 per cohort) were used as a decoy to reduce bias and not for statistical comparisons. Thirty participants (20 men) were treated for 13 (12-14) days. No serious adverse events during the study were recorded. All clinical or laboratory parameters at day 14 compared with baseline suggested clinical stability without significant within-group differences in the dapansutrile-pooled group or the 3 dapansutrile cohorts. Improvements in left ventricular EF [from 31.5% (27.5-39) to 36.5% (27.5-45), P = 0.039] and in exercise time [from 570 (399.5-627) to 616 (446.5-688) seconds, P = 0.039] were seen in the dapansutrile 2000 mg cohort. Treatment with dapansutrile for 14 days was safe and well tolerated in patients with stable HFrEF.