Effects of Empagliflozin in Women and Men With Heart Failure and Preserved Ejection Fraction.

BACKGROUND: Women and men with heart failure (HF) and preserved ejection fraction may differ in their clinical characteristics and their response to therapy. The aim of this study was to evaluate the influence of sex on the effects of empagliflozin in patients with HF and preserved ejection fraction enrolled in the EMPEROR-Preserved trial (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction). METHODS: The effects of empagliflozin on the primary outcome of cardiovascular death or hospitalization for HF and on secondary outcomes (including total HF hospitalization, cardiovascular and all-cause mortality, and Kansas City Cardiomyopathy Questionnaire scores) were compared in women and men in the overall cohort and in subgroups defined by left ventricular ejection fraction (41%-49%, 50%-59%, and ≥60%). The effects of empagliflozin on physiological measures, including changes in systolic blood pressure, uric acid, hemoglobin, body weight, and natriuretic peptide levels, were also assessed. RESULTS: Of the 5988 patients randomized, 2676 (44.7%) were women. In the placebo arm, women tended to have lower risk for adverse outcomes, including a lower risk of all-cause mortality (hazard ratio, 0.69 [95% CI, 0.56, 0.84]). Compared with placebo, empagliflozin reduced the risk of cardiovascular death or hospitalization for HF to a similar degree in both sexes (hazard ratio, 0.81 [95% CI, 0.69, 0.96] for men; and hazard ratio, 0.75 [95% CI, 0.61, 0.92] for women; Pinteraction=0.54). Sex did not modify the relationship between empagliflozin and outcomes across ejection fraction groups. Similar results were seen for secondary outcomes and physiological measures. Compared with placebo, empagliflozin improved the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score to a similar extent in both sexes (1.38 for men versus 1.63 for women at 52 weeks; Pinteraction=0.77); the results were similar for Kansas City Cardiomyopathy Questionnaire overall summary score and total summary score. CONCLUSIONS: Empagliflozin produced similar benefits on outcomes and health status in women and men with HF and preserved ejection fraction. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03057951.

Inconsistent Outcome Reporting in Heart Failure Randomized Controlled Trials.

BACKGROUND: Randomized controlled trials (RCTs) may report outcomes different from those prespecified on trial-registration websites, protocols and statistical analysis plans (SAPs). This study sought to investigate the prevalence and characteristics of heart failure (HF) RCTs that report outcomes different from those prespecified. METHODS AND RESULTS: MEDLINE via PubMed was searched to include phase II-IV HF RCTs in 9 high-impact journals from 2010 to 2020. Outcomes reported in trial publications were compared with prespecified outcomes in protocols, registration websites and SAPs. We used the χ2 or Fisher exact test to analyze correlations between trial characteristics and inconsistencies. Among 216 trials, 32 inconsistencies were observed in 28 trials (13.0%). Among 32 inconsistencies, 2 (6.3%) pertained to omission of prespecified primary outcomes, 4 (12.5%) to omission of prespecified secondary outcomes, 2 (6.3%) to changing prespecified primary outcomes to secondary outcomes, and 2 (6.3%) to changing prespecified secondary outcomes to primary outcomes. Of the inconsistencies, 3 (9.4%) pertained to addition of new primary outcomes, 17 (53.1%) to addition of new secondary outcomes, and 2 (6.3%,) to changes in the timing of assessment of primary outcomes. The majority of the inconsistencies favored statistically significant findings; 78 (36.1%) were registered retrospectively. Single-center recruitment was associated with outcome inconsistencies (ß = -0.14; 95% CI, -0.22 - -0.01; P = 0.035). CONCLUSIONS: More than 1 in 10 trials reported outcomes inconsistent with those specified in trial registration websites, SAPs and protocols. An action plan is warranted to minimize selective reporting and improve transparency.

Patiromer for the management of hyperkalemia in heart failure with reduced ejection fraction: the DIAMOND trial.

AIMS: To investigate the impact of patiromer on the serum potassium level and its ability to enable specified target doses of renin-angiotensin-aldosterone system inhibitor (RAASi) use in patients with heart failure and reduced ejection fraction (HFrEF). METHODS AND RESULTS: A total of 1642 patients with HFrEF and current or a history of RAASi-related hyperkalemia were screened and 1195 were enrolled in the run-in phase with patiromer and optimization of the RAASi therapy [≥50% recommended dose of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, and 50 mg of mineralocorticoid receptor antagonist (MRA) spironolactone or eplerenone]. Specified target doses of the RAASi therapy were achieved in 878 (84.6%) patients; 439 were randomized to patiromer and 439 to placebo. All patients, physicians, and outcome assessors were blinded to treatment assignment. The primary endpoint was between-group difference in the adjusted mean change in serum potassium. Five hierarchical secondary endpoints were assessed. At the end of treatment, the median (interquartile range) duration of follow-up was 27 (13-43) weeks, the adjusted mean change in potassium was +0.03 mmol/l in the patiromer group and +0.13 mmol/l in the placebo group [difference in the adjusted mean change between patiromer and placebo: -0.10 mmol/l (95% confidence interval, CI -0.13, 0.07); P < 0.001]. Risk of hyperkalemia >5.5 mmol/l [hazard ratio (HR) 0.63; 95% CI 0.45, 0.87; P = 0.006), reduction of MRA dose (HR 0.62; 95% CI 0.45, 0.87; P = 0.006), and total adjusted hyperkalemia events/100 person-years (77.7 vs. 118.2; HR 0.66; 95% CI 0.53, 0.81; P < 0.001) were lower with patiromer. Hyperkalemia-related morbidity-adjusted events (win ratio 1.53, P < 0.001) and total RAASi use score (win ratio 1.25, P = 0.048) favored the patiromer arm. Adverse events were similar between groups. CONCLUSION: Concurrent use of patiromer and high-dose MRAs reduces the risk of recurrent hyperkalemia (ClinicalTrials.gov: NCT03888066).

Optical coherence tomography versus angiography and intravascular ultrasound to guide coronary stent implantation: A systematic review and meta-analysis.

BACKGROUND: Optical coherence tomography (OCT) is an adjunct to angiography-guided coronary stent placement. However, in the absence of dedicated, appropriately powered randomized controlled trials, the impact of OCT on clinical outcomes is unclear. OBJECTIVE: To conduct a systematic review and meta-analysis of all available studies comparing OCT-guided versus angiography-guided and intravascular ultrasound (IVUS)-guided coronary stent implantation. METHODS: MEDLINE and Cochrane Central were queried from their inception through July 2022 for all studies that sought to compare OCT-guided percutaneous coronary intervention (PCI) to angiography-guided and IVUS-guided PCI. The primary endpoint was minimal stent area (MSA) compared between modalities. Clinical endpoints of interest were all-cause and cardiovascular mortality, major adverse cardiovascular events (MACE), myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), and stent thrombosis (ST). Risk ratios (RRs) and mean differences (MDs) with their corresponding 95% confidence intervals (CIs) were pooled using a random-effects model. RESULTS: Thirteen studies (8 randomized control trials and 5 observational studies) enrolling 6312 participants were included. OCT was associated with a strong trend toward increased MSA compared to angiography (MD = 0.36, p = 0.06). OCT-guided PCI was also associated with a reduction in the incidence of all-cause mortality [RR = 0.59, 95% CI (0.35, 0.97), p = 0.04] and cardiovascular mortality [RR = 0.41, 95% CI (0.21, 0.80), p = 0.009] compared with angiography-guided PCI. Point estimates favored OCT relative to angiography in MACE [RR = 0.75, 95% CI (0.47, 1.20), p = 0.22] and MI [RR = 0.75, 95% CI (0.53, 1.07), p = 0.12]. No differences were detected in ST [RR = 0.71, 95% CI (0.21, 2.44), p = 0.58], TLR [RR = 0.71, 95% CI (0.17, 3.05), p = 0.65], or TVR rates [RR = 0.89, 95% CI (0.46, 1.73), p = 0.73]. Compared with IVUS guidance, OCT guidance was associated with a nonsignificant reduction in the MSA (MD = -0.16, p = 0.27). The rates of all-cause and cardiovascular mortality, MACE, MI, TLR, TVR, or ST were similar between OCT-guided and IVUS-guided PCI. CONCLUSIONS: OCT-guided PCI was associated with reduced all-cause and cardiovascular mortality compared to angiography-guided PCI. These results should be considered hypothesis generating as the mechanisms for the improved outcomes were unclear as no differences were detected in the rates of TLR, TVR, or ST. OCT- and IVUS-guided PCI resulted in similar post-PCI outcomes.

Safety and efficacy of transcatheter aortic valve replacement for native aortic valve regurgitation: A systematic review and meta-analysis.

OBJECTIVE: The objective of this study was to analyze the available literature on using transcatheter aortic valve replacement (TAVR) for native aortic regurgitation (AR). BACKGROUND: Surgical aortic valve replacement is the gold standard therapy for native AR. TAVR has emerged as an alternative approach in high-risk patients. METHODS: MEDLINE, Scopus, and Cochrane CENTRAL were searched for reports of at least 5 patients undergoing TAVR for native AR. Outcomes included 30-day mortality, myocardial infarction, stroke, major bleeding, postprocedural moderate to severe AR, and device success. Pooled estimates were calculated using a random-effects model. Subgroup analysis and a meta-regression were performed to study the effects of study level covariates on outcomes. RESULTS: Nineteen studies (n =998 patients) were included. The rate of procedural success per Valve Academic Research Consortium - 2 (VARC-2) criteria was 86.2% (78.8%-92.2%]. Thirty-day mortality was 11.9% (9.4%-14.7%). Subgroup analysis showed the use of new generation valves was associated with lower 30-day mortality (P = 0.02) and higher device success (P = 0.009) compared with early generation valves. There was no significant difference (P = 0.13) in the rate of 30-day mortality between patients receiving purpose-specific [8.2% (4.3%-13.1%); I2 = 0%] and nonpurpose specific valves [13.0% (8.2%-18.6%); I2 = 25%]. However, device success was higher (P = 0.02) in patients who received purpose-specific valves [96.3% (92.2%-98.9%); I2 = 0%] compared with nonpurpose specific valves [84.4% (75%-91.9%); I2 =46%]. CONCLUSION: TAVR for native AR is associated with acceptable procedural success but increased early mortality. However, the safety and the efficacy of the procedure increased with newer valves.

Percutaneous Mitral Valve Repair versus Optimal Medical Therapy in Patients with Functional Mitral Regurgitation: A Systematic Review and Meta-Analysis.

OBJECTIVES: To compare percutaneous mitral valve repair (PMVR) with optimal medical therapy (OMT) in patients with heart failure (HF) and severe functional mitral regurgitation (FMR). BACKGROUND: Many patients with HF and FMR are not suitable for surgical valve replacement and remain symptomatic despite maximal OMT. PMVR has recently emerged as an alternative solution. METHODS: We performed a systematic review and a meta-analysis to address this question. Cochrane CENTRAL, MEDLINE, and Scopus were searched for randomized (RCT) and nonrandomized studies comparing PMVR with OMT in patients with HF and FMR. Primary endpoint was all-cause midterm mortality (at 1 and 2 years). Secondary endpoints were 30-day mortality and cardiovascular mortality and HF hospitalizations, at maximum follow-up. Studies including mixed cohort of degenerative and functional MR were allowed initially but were excluded in a secondary sensitivity analysis for each of the study's end points. This meta-analysis was performed following the publication of two RCTs (MITRA-FR and COAPT). RESULTS: Eight studies (six observational, two RCTs) comprising 3,009 patients were included in the meta-analysis. In comparison with OMT, PMVR significantly reduced 1-year mortality (RR: 0.70 [0.56, 0.87]; p=0.002; I2=47.6%), 2-year mortality (RR: 0.63 [0.55, 0.73]; p<0.001; I2=0%), and cardiovascular mortality (RR: 0.32 [0.23, 0.44]; p<0.001; I2=0%). No significant difference between PMVR+OMT and OMT was noted in HF hospitalization (HR: 0.69 [0.40, 1.20]; p=0.19; I2=85%) and 30-day mortality (RR: 1.13 [0.68, 1.87]; p=0.16; I2=0%). CONCLUSIONS: In comparison with OMT, PMVR significantly reduces 1-year mortality, 2-year mortality, and cardiovascular mortality in patients with HF and severe MR.

Association of low diastolic blood pressure with cardiovascular outcomes and all-cause mortality: A meta-analysis.

BACKGROUND: Reduction of diastolic blood pressure (DBP) below 70 mmHg may decrease perfusion to the heart and worsen cardiovascular (CV) outcomes. AIMS: Explore the association between low DBP and CV outcomes. METHODS: We searched the online databases until August 2023 for studies reporting the risk of all-cause mortality (ACM) or CV outcomes in patients with low versus normal DBP (70-80mm Hg). RESULTS: Inclusion of 10 studies (n = 1,998,223 patients) found that a mean achieved DBP < 60 mmHg was associated with an increased risk of all-cause mortality (HR 1.48; 95 % CI [1.26-1.74]), especially in patients with pre-existing CV disease. It was also associated to a higher risk of major adverse cardiovascular events (HR 1.84; [1.28-2.65]) and myocardial infarction (HR 1.49; [1.13-1.97]). A DBP of 60-69 mmHg was associated with an increased risk of all-cause mortality (HR 1.11; [1.03-1.20]). CONCLUSION: Reduction of DBP, particularly below 60 mmHg, is associated with increased risk of ACM.

Role of telemedicine in the management of obesity: State-of-the-art review.

Obesity is a worsening public health epidemic that remains challenging to manage. Obesity substantially increases the risk of cardiovascular diseases and presents a significant financial burden on the healthcare system. Digital health interventions, specifically telemedicine, may offer an attractive and viable solution for managing obesity. During the COVID-19 pandemic, the need for a safer alternative to in-person visits led to the increased popularity of telemedicine. Multiple studies have tested the efficacy of telemedicine modalities, including digital coaching via videoconferencing sessions, e-health monitoring using wearable devices, and asynchronous forms of communication such as online chatrooms with counselors. In this review, we discuss the available evidence for telemedicine interventions in managing obesity, review current challenges and barriers to using telemedicine, and outline future directions to optimize the management of patients with obesity using telemedicine.

Effect of vitamin D on postoperative atrial fibrillation in patients who underwent coronary artery bypass grafting: A systematic review and meta-analysis.

BACKGROUND: Vitamin D insufficiency/deficiency has been identified as a risk factor for postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG). This is associated with significantly increased morbidity and mortality leading to not only prolonged hospital and intensive care unit (ICU) stay, but increased risk of stroke, heart failure, dementia, and long-term atrial fibrillation. This analysis aims to evaluate the efficacy of vitamin D supplementation in preventing POAF in patients undergoing CABG. METHODS: We searched PubMed, Cochrane Central Register of Controlled Trials and SCOPUS from inception to June 2022 for randomized controlled trials (RCTs). The outcome of interest was the incidence of POAF. Secondarily, we analyzed the length of ICU stay, length of hospital stay, cardiac arrest, cardiac tamponade, and blood transfusion. Results were pooled using a random-effect model. Three RCTs consisting of 448 patients were included. RESULTS: Our results suggest that vitamin D significantly reduced the incidence of POAF (RR: 0.60; 95 % CI: 0.40, 0.90; p = 0.01; I2 = 8 %). It was also observed that vitamin D significantly reduced the duration of ICU stay (WMD: -1.639; 95 % CI: -1.857, -1.420; p < 0.00001). Furthermore, the length of hospital stay (WMD: -0.85; 95 % CI: -2.14, 0.43; p = 0.19; I2 = 87 %) was also reduced, however, the result was not significant. CONCLUSION: Our pooled analysis suggests that vitamin D prevents POAF. Future large-scale randomized trials are needed to confirm our results.

An Individual Patient-Level Meta-Analysis of Ischemic Versus Nonischemic Cardiomyopathy and Trajectory of Decongestion in Patients With Acute Decompensated Heart Failure.

Data are limited regarding the impact of ischemic cardiomyopathy (ICM) or non-ICM (NICM) on the trajectory of in-hospital decongestion among patients with acute decompensated heart failure (ADHF). Therefore, we aimed to assess the course of decongestion among patients admitted for ADHF by history of ICM and NICM. Patients included in the DOSE (Diuretic strategies in patients with acute decompensated heart failure), ROSE (ROSE acute heart failure randomized trial), and Ultrafiltration in decompensated heart failure with cardiorenal syndrome (CARRESS-HF) trials of patients with ADHF were categorized into ICM and NICM based on history. Among 762 patients included in our meta-analysis, 433 (56.8%) had a history of ICM. Patients with ICM were older (70.8 vs 63.9 years; p ≤0.001) and had higher rates of co-morbidities. After covariate adjustment, there was no significant differences between NICM and ICM regarding net fluid loss (4,952 vs 4,384 ml, p = 0.81) or mean change in serum N-terminal pro-brain natriuretic peptide (-2,162 vs -1,809 pg/ml, p = 0.092). Mean change in weight showed modest improvement in favor of patients with NICM, but this did not meet statistical significance (-8.24 vs -7.70 pounds, p = 0.068). After adjustment, there was no significant difference in the risk of 60-day composite all-cause mortality or hospitalization for HF among those with ICM versus NICM. Among patients with left ventricular ejection fraction <40%, NICM was associated with higher scoring on global sense of well-being (global visual analog scale; +25.5 vs +19.1, p = 0.023) and improvement in serum creatinine (-0.031 mg/100 ml vs +0.042 mg/100 ml, p = 0.009) at 72 hours. Among patients with left ventricular ejection fraction >40%, NICM was associated with decreased scoring on global visual analog scale at 72 hours (+15.7 vs +21.2, p = 0.049). In conclusion, more than half of the patients admitted for ADHF had ICM. History of ICM was not independently associated with a difference in course of decongestion, self-assessment of well-being and dyspnea, or short-term clinical outcomes.

Clinical Outcomes in Hypertensive Emergency: A Systematic Review and Meta-Analysis.

Background To study the prevalence and types of hypertension-mediated organ damage and the prognosis of patients presenting to the emergency department (ED) with hypertensive emergencies. Methods and Results PubMed was queried from inception through November 30, 2021. Studies were included if they reported the prevalence or prognosis of hypertensive emergencies in patients presenting to the ED. Studies reporting data on hypertensive emergencies in other departments were excluded. The extracted data were arcsine transformed and pooled using a random-effects model. Fifteen studies (n=4370 patients) were included. Pooled analysis demonstrates that the prevalence of hypertensive emergencies was 0.5% (95% CI, 0.40%-0.70%) in all patients presenting to ED and 35.9% (95% CI, 26.7%-45.5%) among patients presenting in ED with hypertensive crisis. Ischemic stroke (28.1% [95% CI, 18.7%-38.6%]) was the most prevalent hypertension-mediated organ damage, followed by pulmonary edema/acute heart failure (24.1% [95% CI, 19.0%-29.7%]), hemorrhagic stroke (14.6% [95% CI, 9.9%-20.0%]), acute coronary syndrome (10.8% [95% CI, 7.3%-14.8%]), renal failure (8.0% [95% CI, 2.9%-15.5%]), subarachnoid hemorrhage (6.9% [95% CI, 3.9%-10.7%]), encephalopathy (6.1% [95% CI, 1.9%-12.4%]), and the least prevalent was aortic dissection (1.8% [95% CI, 1.1%-2.8%]). Prevalence of in-hospital mortality among patients with hypertensive emergency was 9.9% (95% CI, 1.4%-24.6%). Conclusions Our findings demonstrate a pattern of hypertension-mediated organ damage primarily affecting the brain and heart, substantial cardiovascular renal morbidity and mortality, as well as subsequent hospitalization in patients with hypertensive emergencies presenting to the ED.

Trajectory of Decongestion and Mortality in Young Adults with Acute Heart Failure.

Although the prevalence of HF in young adults (age <50 years) is increasing, there are limited data on the trajectory of decongestion and short-term outcomes in young adults with acute heart failure (AHF). We pooled patients from 3 randomized trials of AHF conducted within the Heart Failure Network (the Diuretic Optimization Strategies trial, the Renal Optimization Strategies Trial, and the Cardiorenal Rescue Study in Acute Decompensated Heart Failure). The association between young age (<50 years and >50 years) and in-hospital changes in various measures of decongestion as well as short-term outcomes including risk for rehospitalization, and all-cause mortality was evaluated. Of 762 patients, 72 (10.3%) patients were young. Young adults were more likely to be African American (53.8% vs 19.3%), to have a lower rate of ischemic HF etiology (25.6% vs 60.4%, P <0.001), and a lower burden of hypertension, chronic kidney disease and atrial fibrillation. Young adults had a lower left ventricular ejection fraction (median 20% vs 33%, P < 0.001); they had a higher admission weight (median 242.7 lbs vs 201.5 lbs, P < 0.001), but lower NT-pro BNP levels (median 3622 pg/mL vs 4676 pg/mL, P = 0.003). After covariate adjustment, there was no difference in the change in NT-pro BNP (P = 0.25), net fluid loss (P = 0.42), or renal function (P = 0.56) between young and older adults by 72 or 96 hours of randomization. There was no difference in orthodema congestion score or the composite clinical endpoint during the follow-up (all-cause mortality or any rehospitalization) (adjusted odds ratios (95% confidence intervals): 2.51 (0.78-8.01), P = 0.12). In this pooled analysis of 3 clinical trial cohorts, compared with older adults, younger adults had a unique demographic and clinical profile. Despite these differences, there was no difference by age group in in-hospital decongestion or post-discharge readmission or mortality.

Is it safe and effective to administer COVID-19 vaccines during pregnancy? A systematic review and meta-analysis.

OBJECTIVE: To evaluate the safety and efficacy of COVID-19 vaccines in pregnant women performing an updated meta-analysis. METHODS: We searched PubMed, Cochrane Central, and SCOPUS from inception to March 2022. Outcomes of interest were incidence of adverse maternal, fetal and neonatal consequences pertaining to safety of the vaccines. Secondarily, we analyzed the number of SARS-CoV-2 infections, hospitalization for COVID-19, and admission to the I.C.U. for COVID-19 assessing the effectiveness of vaccines. Results were pooled using a random effects model. RESULTS: Ten observational studies (n=326,499) analyzing pregnant women were included. Our results suggest that COVID-19 vaccination prevents infection (OR: 0.56, 95% CI: 0.47, 0.67; P = <0.00001) and related hospitalizations (OR: 0.50, 95% CI: 0.31, 0.82; P = 0.006) effectively. It was also observed that vaccination does not change adverse outcomes in pregnancy, namely preeclampsia or eclampsia, stroke (four weeks of delivery), meconium-stained amniotic fluid, spontaneous vaginal delivery, operative vaginal delivery, cesarean delivery, postpartum hemorrhage, and blood transfusions. Furthermore, the vaccine was observed to be protective against neonatal COVID-19 I.C.U. admissions (OR: 0.85; 95% CI: 0.81, 0.90; P = <0.00001). CONCLUSION: Our pooled analysis suggests that the COVID-19 vaccination in pregnant women prevents infection effectively and has no adverse outcomes. Future large-scale trials in a randomized fashion are needed to confirm our results.

Efficacy of Empagliflozin in Patients With Heart Failure Across Kidney Risk Categories.

BACKGROUND: Empagliflozin reduces the risk of major heart failure outcomes in heart failure with reduced or preserved ejection fraction. OBJECTIVES: The goal of this study was to evaluate the effect of empagliflozin across the spectrum of chronic kidney disease in a pooled analysis of EMPEROR-Reduced and EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced or Preserved Ejection Fraction, respectively). METHODS: A total of 9,718 patients were grouped into Kidney Disease Improving Global Outcomes (KDIGO) categories based on estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio into low-, moderate-, high-, and very-high-risk categories, comprising 32.0%, 29.1%, 21.9%, and 17.0% of the participants, respectively. RESULTS: In the placebo arm, when compared with lower risk categories, patients at higher risk experienced a slower rate of decline in eGFR, but a higher risk of a composite kidney event. Empagliflozin reduced the risk of cardiovascular death or heart failure hospitalizations similarly in all KDIGO categories (HR: 0.81; 95% CI: 0.66-1.01 for low-; HR: 0.63; 95% CI: 0.52-0.76 for moderate-; HR: 0.82; 95% CI: 0.68-0.98 for high-; and HR: 0.84; 95% CI: 0.71-1.01 for very-high-risk groups; P trend = 0.30). Empagliflozin reduced the rate of decline in eGFR whether it was estimated by chronic slope, total slope, or unconfounded slope. When compared with the unconfounded slope, the magnitude of the effect on chronic slope was larger, and the effect on total slope was smaller. In EMPEROR-Reduced, patients at lowest risk experienced the largest effect of empagliflozin on eGFR slope; this pattern was not observed in EMPEROR-Preserved. CONCLUSIONS: The benefit of empagliflozin on major heart failure events was not influenced by KDIGO categories. The magnitude of the renal effects of the drug depended on the approach used to calculate eGFR slopes.

High-Intensity Interval Training Versus Moderate Continuous Training in Patients With Heart Failure With Preserved Ejection Fraction: A Systematic Review and Meta-analysis.

High-intensity interval training (HIIT) is a novel training approach that improves cardiopulmonary fitness and functional capacity in numerous chronic conditions, however its impact in patients with heart failure (HF) with preserved ejection fraction (HFpEF) is uncertain. We evaluated data from prior studies reporting the effects of HIIT versus moderate continuous training (MCT), on cardiopulmonary exercise outcomes in patients with HFpEF. PubMed and SCOPUS were queried from inception till February 1st, 2022 for all randomized controlled trials (RCT) comparing the effect of HIIT versus MCT in patients with HFpEF on peak oxygen consumption (peak VO2), left atrial volume index (LAVI), respiratory exchange ratio (RER), and ventilatory efficiency (VE/CO2 slope). A random-effects model was applied, and the weighted mean difference (WMD) of each outcome was reported with 95% confidence intervals (CI). Three RCTs (total N = 150 patients with HFpEF), with a follow-up of 4 to 52 weeks were included in our analysis. Our pooled analysis demonstrated that HIIT significantly improved peak VO2 (WMD = 1.46 mL/kg/min (0.88, 2.05); P < 0.00001; I2 = 0%), as compared to MCT. However, no statistically significant change was demonstrated for LAVI (WMD = -1.71 mL/m2 (-5.58, 2.17); P = 0.39; I2 = 22%), RER (WMD = -0.10 (-0.32, 0.12); P = 0.38; I2 = 0%), and VE/CO2 slope (WMD = 0.62 (-1.99, 3.24); P = 0.64; I2 = 67%) in patients with HFpEF. Across current RCT data, HIIT, compared to MCT, had a significant impact on improving peak VO2. Conversely, there was no significant change in LAVI, RER, and VE/CO2 slope between HFpEF patients undertaking HIIT as opposed to MCT.

Effect of SGLT2 Inhibitors on Cardiovascular Outcomes Across Various Patient Populations.

BACKGROUND: The effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on heart failure (HF) outcomes and cardiovascular (CV) death in patients with varying combinations of type 2 diabetes mellitus (T2DM), HF, and chronic kidney disease (CKD) are uncertain. OBJECTIVES: The authors conducted a meta-analysis assessing the effects of SGLT2 inhibitors on HF outcomes and CV death across different patient populations. METHODS: Online databases were queried up to November 2022 for primary and secondary analyses of trials of SGLT2 inhibitors in patients with HF, T2DM, or CKD. Outcomes of interest were composite of first heart failure hospitalization (HFH) or CV death (first HFH/CV death), first HFH, and CV death. Data were pooled by means of a random-effects model to derive HRs and 95% CIs. RESULTS: Thirteen trials (n = 90,413) were included. Compared with placebo, SGLT2 inhibitors reduced the risk of first HFH/CV death by 24% in HF (HR: 0.76; 95% CI: 0.72-0.81), 23% in T2DM (HR: 0.77; 95% CI: 0.73-0.81), and 23% in CKD (HR: 0.77; 95% CI: 0.72-0.82). The benefit was consistent in HF with reduced or preserved ejection fraction, HF with or without T2DM, and HF with or without CKD. The benefit was also consistent in T2DM with or without CKD, T2DM without HF, CKD without HF, and in patients with all 3 comorbidities. SGLT2 inhibitors significantly reduced CV death by 16% in HF, 15% in T2DM, and 12% in CKD. CONCLUSIONS: SGLT2 inhibitors reduce HF events and CV death in cohorts of HF, T2DM and CKD, and these effects appear consistent in patients with varying combinations of these diseases.

Health status across major subgroups of patients with heart failure and preserved ejection fraction.

AIMS: There are limited data on health status and changes in it over time across major subgroups of patients with heart failure and preserved ejection fraction (HFpEF), including ejection fraction spectrum, age, sex, region, body mass index (BMI), and comorbidities including diabetes, chronic kidney disease (CKD), anaemia, and atrial fibrillation/flutter. METHODS AND RESULTS: In the EMPEROR-Preserved trial, the Kansas City Cardiomyopathy Questionnaire (KCCQ) was assessed at baseline, 12, 32 and 52 weeks. Determinants of baseline KCCQ score and change over time, and the impact of empagliflozin on KCCQ scores were studied in specified subgroups. A Cox model was used to assess the association between 5- and 10-point increase and 5-point decrease in KCCQ score from baseline to week 12 and later outcomes. Among 2979 participants in the placebo arm, mean KCCQ clinical summary score (CSS) was 70.7 (20.8). Older age, female sex, BMI, anaemia, and a history of diabetes, and CKD were associated with worse scores. KCCQ-CSS score improved during follow-up; patients with atrial fibrillation/flutter at enrollment (p trend = 0.014) and CKD (p trend < 0.001) had less improvement. A 5-point increase in KCCQ-CSS at week 12 was associated with lower risk of cardiovascular death or heart failure hospitalization (5%), cardiovascular death (8%), and first heart failure hospitalization (4%) subsequently. A similar trend was seen with KCCQ total symptom score (TSS) and overall summary score (OSS). Empagliflozin improved KCCQ-CSS, -TSS and -OSS scores similarly across subgroups studied except for greater improvement in patients with the highest BMI (p trend = 0.153, 0.08 and 0.078, respectively). CONCLUSION: Health status in patients with HFpEF is impaired, especially in elderly, women, and those with obesity and comorbidities. Empagliflozin improved health status among all key subgroups studied with a greater effect in obese patients.