Association of Coronary Microvascular Dysfunction With Heart Failure Hospitalizations and Mortality in Heart Failure With Preserved Ejection Fraction: A Follow-up in the PROMIS-HFpEF Study

BackgroundCoronary microvascular dysfunction (CMD) is common in heart failure with preserved ejection fraction (HFpEF). We assessed the association of CMD with hospitalization and mortality in HFpEF.Methods and ResultsWe assessed the 1-year outcomes in patients from the PROMIS-HFpEF study, a prospective observational study of patients with chronic stable HFpEF undergoing coronary flow reserve measurements. Outcomes were (1) time to cardiovascular (CV) death/first HF hospitalization, (2) CV death/recurrent HF hospitalizations, (3) all-cause death/first HF hospitalization, and (4) first and (5) recurrent all-cause hospitalizations. CMD was defined as coronary flow reserve of <2.5. Time to CV death/first hospitalization was compared by log-rank test and recurrent HF and all-cause hospitalizations by Poisson test. Of 263 patients enrolled, 257 were evaluable at 1 year. Where the coronary flow reserve was interpretable (n = 201), CMD was present in 150 (75%). The median follow-up was 388 days (Q1, Q3 365, 418). The outcome of CV death/first HF hospitalization occurred in 15 patients (4 CV deaths). The incidence rate was in CMD 96 per 1000 person-years, 95% confidence interval 54–159, vs non-CMD 0 per1000 person-years, 95% confidence interval 0–68, P = .023, and remained significant after accounting for selected clinical variables. In patients with CMD, the incidence rates were significantly higher also for CV death/recurrent HF hospitalizations, all-cause death/first HF, and recurrent but not first all-cause hospitalization.ConclusionsIn this exploratory assessment of the prognostic role of CMD in HFpEF, CMD was independently associated with primarily CV- and HF-specific events. The high prevalence of CMD and its CV and HF specific prognostic role suggest CMD may be a potential treatment target in HFpEF.     

Heart Failure With Recovered Ejection Fraction in African Americans: Results From the African-American Heart Failure Trial

Background

Recent studies have described the entity of heart failure with recovered ejection fraction (HFrecEF), but population-specific studies remain lacking. The aim of this study was to characterize patients enrolled in the African-American Heart Failure Trial (A-HeFT) who had significant improvement in their ejection fraction (EF) during the 1st 6 months of follow-up.

Patient Characteristics and Outcomes of Type 2 Myocardial Infarction During Heart Failure Hospitalizations in the United States

BackgroundType 2 myocardial infarction (MI) is increasingly diagnosed in patients with heart failure (HF). A paucity of data exists pertinent to the contemporary prevalence and impact of type 2 MI in patients with HF. We studied the patient profiles and the prognostic impact of type 2 MI on outcomes of HF hospitalizations.MethodsThe Nationwide Readmission Database 2018 was queried for patients with HF hospitalizations with and without type 2 MI. Baseline characteristics, inpatient outcomes, and 30-day all-cause readmissions between both cohorts were compared.ResultsOf 1,072,674 primary HF hospitalizations included in the study, 28,813 (2.7%) had type 2 MI. Patients with type 2 MI were more likely to be males (56.5% vs 51.6%; P < .001) and had a higher prevalence of hypertension (94% vs 92.2%; P < .001), prior myocardial infarction (17.1% vs 14.9%; P < .001), anemia (9.1% vs 8.1%; P < .001), chronic kidney disease (55.7% vs 49.4%; P < .001), neurological disorders (9.4% vs 7.3%; P < .001), and weight loss (7.3% vs 5.6%; P < .001). Compared with their counterparts without type 2 MI, patients with HF with type 2 MI had significantly higher in-hospital mortality (adjusted odds ratio [aOR], 1.53; 95% confidence interval [CI], 1.37-1.72), hospital costs (adjusted parameter estimate, $1785; 95% CI, 1388-2182), discharge to nursing facility (aOR, 1.22; 95% CI, 1.15-1.29), longer length of stay (adjusted parameter estimate, 0.53; 95% CI, 0.42-0.64), and rate of 30-day all-cause readmissions (aOR, 1.06; 95% CI, 1.01-1.12).ConclusionType 2 MI in patients hospitalized with HF is associated with higher mortality and resource utilization in the United States.     

Can Medications be Safely Withdrawn in Patients With Stable Chronic Heart Failure? Systematic Review and Meta-analysis

BackgroundHeart failure (HF) therapy involves use of multiple medications. There is little guidance on the safety and impact on clinical outcomes of stopping HF medications.Methods and ResultsA comprehensive systematic search for studies of drug therapy withdrawal in HF was performed. Meta-analysis of the risk ratio (RR) was performed with the use of the Mantel-Haenszel random effects model for all-cause mortality and cardiovascular outcomes. Twenty-six studies met the inclusion criteria. Studies on withdrawal of renin-angiotensin-aldosterone system (RAAS) inhibitors and beta-blockers in HF are scarce and small, yet show relatively convincingly that such withdrawals have untoward effects on cardiac structure, symptoms, and major outcomes. Meta-analysis of 7 studies of digoxin withdrawal (2,987 participants) without background beta-blocker showed increased HF hospitalizations (RR 1.30, 95% confidence interval [CI] 1.16–1.46; P < .0001), but no impact on all-cause mortality (RR 1.00, 95% CI 0.90–1.12; P = .06) nor reduction in all-cause hospitalization (RR 1.03, 95% CI 0.98–1.09; P = .27). Diuretic withdrawal trials demonstrated an ongoing need for these agents in chronic HF. Studies in peripartum cardiomyopathy showed that medications could be successfully withdrawn after recovery.ConclusionCurrent evidence discourages any attempt to discontinue RAAS inhibitors or beta-blockers in patients with stable HF, regardless of clinical and/or echocardiographic status. Formal withdrawal trials of other classes are needed.     

COLIGENTA treatment of small intestinal bacterial overgrowth. Results of an open study.

PurposeThe treatment of small intestinal overgrowth (SIBO) varies according to the center. The present study aimed to evaluate the efficacy of COLIGENTA, an association of colimycin and gentamycin, on SIBO symptomatology and breath test normalizationPatients and MethodsIn this prospective cross-sectional open study, 150 patients with functional bowel disorders and SIBO diagnosed by lactulose hydrogen breath test (LHBT) underwent COLIGENTA oral treatment. A new HLBT was performed 4 weeks after the first HLBT.ResultsThe patients were mainly female (74%), with a mean age of 47.4 ± 16.2 years and a body mass index of 26.2 ± 5.9 kg/m². After treatment, a decrease of expired hydrogen concentration (P<0.001) was found in the entire population. Improvement of gastrointestinal symptoms was found in 129 patients (86%), while the breath test's normalization was found in 62 patients (42%). Logistic regression showed that normalization of bowel symptoms was not associated with demographics, clinical, or hydrogen breath concentration. In contrast, normalization of LHBT was associated with an increase of breath hydrogen concentration at time 100 min during the first test (P = 0.003; OR=1.072; 95%CI= [1.023–1.123]).ConclusionThe present study shows that 10-days of COLIGENTA treatment has a high SIBO clinical improvement rate and can be used as the first or second treatment line.     

Percutaneous Mitral Valve Repair Vs. Stand-Alone Medical Therapy in Patients with Functional Mitral Regurgitation and Heart Failure

BackgroundFunctional mitral regurgitation (FMR) is a common finding among patients with heart failure (HF) and it is related to adverse events. Outcomes in patients undergoing transcatheter mitral valve repair (TMVR) are still a matter of debate. We performed a meta-analysis to assess mid- and long-term outcomes of patients with FMR treated with MitraClip® compared to medical management.MethodsWe conducted an electronic database search of all published data PubMed Central, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and Google Scholar databases. The primary end-point was all-cause mortality. The secondary end-points were hospitalizations for HF, need for heart transplantation or left ventricular assist device, unplanned mitral valve surgery, myocardial infarction and stroke.ResultsFive studies (n = 1513 patients) were included in the analysis. The summary estimate including all the available studies showed a statistically significant reduction in all-cause mortality favoring MitraClip® (HR 0.56, CI 95% [0.38–0.84]) and HF hospitalizations (HR 0.65; CI 95% [0.46–0.92]). A significant reduction in the indication for advanced HF therapies (OR 0.48; CI 95% [0.25–0.90]) or the need for unplanned mitral valve surgery (OR 0.20; CI 95% [0.07–0.57]) was also found in the group of patients that underwent TMVR. No differences in the incidence of myocardial infarction or stroke were found between both groups of treatment. No publication bias was detected.ConclusionTMVR with MitraClip® system was related to a significant reduction in all-cause mortality, hospitalizations for HF and the need for HF transplant, left ventricular assist device or unplanned surgery beyond 1-year follow up.     

Non-coronary cardiac calcifications and outcomes in patients with heart failure

BackgroundCalcium deposits on heart valves are considered a local manifestation of atherosclerosis and are associated with poor cardiovascular outcomes. The clinical significance of cardiac calcifications among heart failure (HF) patients, as assessed by echocardiography, is unknown. This study evaluated associations of cardiac calcifications with mortality and hospital admissions in this specific population.MethodsMedical records of all patients who initiated ambulatory surveillance at our HF clinic during 2011–2018 were reviewed. Calcifications in the aortic valve, aortic root, or the mitral valve were evaluated. Patients with moderate to severe regurgitation or stenosis of the aortic or mitral valves were excluded. The primary endpoint was the composite of long-term all-cause mortality and HF hospitalizations. Secondary endpoints were long-term all-cause mortality and more than one hospitalization due to HF.ResultsThis retrospective study included 814 patients (mean age 70.9 ± 13 years, 63.2% male). Of the total cohort, 350 (43%) had no cardiac calcifications and 464 (57%) had at least 1 calcified site. Considering the patients with no calcification as the reference group yielded a higher adjusted odds ratios for the composite endpoint, all-cause death, and recurrent HF hospitalizations, among patients with any cardiac calcification (OR = 1.68, 95%CI = 1.1–2.5, p = 0.01, OR=1.61, 95%CI = 1.1–2.3, p < 0.01, and OR = 1.50, 95%CI = 1.1–2.2, p < 0.01, respectively).ConclusionsWe found an independent association between cardiac calcifications and the risk of death and HF hospitalizations among ambulatory HF patients. Cardiac calcifications evaluated during routine echocardiography may contribute to the risk stratification of patients with HF.     

Hyponatremia and long-term outcomes in chronic heart failure--an observational study from the Duke Databank for Cardiovascular Diseases

BackgroundHyponatremia is a well known predictor of short-term outcomes in heart failure (HF); however, its impact on long-term survival in HF patients with systolic dysfunction is not well established.Methods and ResultsUsing the Duke Databank for Cardiovascular Diseases, we identified 1,045 patients with HF and systolic dysfunction undergoing cardiac catheterization from January 2000 through December 2008. The effect of hyponatremia as independent predictor of all-cause death and cardiovascular death/rehospitalization was examined using a multivariable Cox proportional regression model. Hyponatremia was present in 107/1,045 patients (10.2%). Hyponatremic patients were older, more likely to be anemic, with higher heart rate and levels of blood urea nitrogen, lower blood pressure, and more severe HF. Using an unadjusted analysis, hyponatremia was associated with higher risk of all-cause death (hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.44–2.49; P < .0001) and of cardiovascular death/rehospitalization (HR 1.40, 95% CI 1.11–1.77; P = .005) at 4.5 years. When entered into a multivariable Cox model, hyponatremia remained significant for all-cause death (HR 1.42, 95% CI 1.07–1.88) and for cardiovascular death/rehospitalization (HR 1.45, 95% CI 1.14–1.86).ConclusionsHyponatremia is relatively common in HF patients with LV dysfunction and is independently associated with increased risk of all-cause mortality and cardiovascular mortality/rehospitalization.     

Association Between Cardiorespiratory Fitness and Risk of Heart Failure: A Meta-Analysis

BackgroundEvidence emerges that cardiorespiratory fitness (CRF) might be implicated in the development of heart failure (HF). This meta-analysis aimed to quantify the association between CRF exposed at baseline and HF risk with dose–response analysis and to assess whether CRF changes over time are correlated with alterations in HF risk.Methods and ResultsCohort studies that assessed the association between CRF and risk of HF in subjects without baseline HF were included. Study-specific multivariate-adjusted relative risks (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Ten studies from 8 articles were included, enrolling 8987 incident HF cases from 154,598 participants. The RR of HF per 1-metabolic equivalent (MET) higher CRF at baseline was 0.82 (95% CI 0.80–0.84) in the overall population. The RRs were similar in men (0.82, 95% CI 0.80–0.85) and women (0.81, 95% CI 0.78–0.84), and remained minorly changed in patients with existing diabetes, hypertension, or cardiovascular disease at entry. No evidence of a nonlinear relationship between CRF at baseline and risk of HF was observed (P_nonlinearity = .18). The RR of HF per 1-MET increase in CRF over time was 0.79 (95% CI 0.67–0.93), and the measurement of CRF provided incremental value to the prediction of HF beyond conventional models.ConclusionsHigh or increased CRF resulted in reduced risk of HF in a dose-dependent manner, supporting the necessity to increase CRF to prevent HF in clinical practice.     

The Influence of Renal Function on Clinical Outcome and Response to β-Blockade in Systolic Heart Failure: Insights From Metoprolol CR/XL Randomized Intervention Trial in Chronic HF (MERIT-HF)

BackgroundLimited information is available on the risk and impact of renal dysfunction on the response to β-blockade and mode of death in systolic heart failure (HF).Methods and ResultsRenal function was estimated with glomerular filtration rate (eGFR) using the simplified Modification of Diet in Renal Disease (MDRD) equation. Patients from the Metoprolol CR/XL Controlled Randomized Intervention Trial in Chronic HF (MERIT-HF) were divided into 3 renal function subgroups (MDRD formula): eGFR_MDRD > 60 (n = 2496), eGFR_MDRD 45 to 60 (n = 976), and eGFR_MDRD < 45 mL/min per 1.73m² body surface area (n = 493). Hazard ratio (HR) was estimated with Cox proportional hazards models adjusted for prespecified risk factors. Placebo patients with eGFR < 45 had significantly higher risk than those with eGFR > 60: HR for all-cause mortality, 1.90 (95% confidence interval [CI], 1.28 to 2.81) comparing placebo patients with eGFR < 45 and eGFR > 60, and for the combined end point of all-cause mortality/hospitalization for worsening HF (time to first event): HR, 1.91 (95% CI, 1.44 to 2.53). No significant increase in risk with deceased renal function was observed for those randomized to metoprolol controlled release (CR)/extended release (XL) due to a highly significant decrease in risk on metoprolol CR/XL in those with eGFR < 45. For total mortality, metoprolol CR/XL vs placebo: HR, 0.41 (95% CI. 0.25 to 0.68; P < .001) in those with eGFR < 45 compared with HR, 0.71 (95% CI, 0.54 to 0.95; P < .021) for those with eGFR > 60; corresponding data for the combined end point was HR, 0.44 (95% CI, 0.31 to 0.63; P < .0001) and HR, 0.75 (0.62 to 0.92; P = .005, respectively; P = .095 for interaction by treatment for total mortality; P = .011 for combined end point). Metoprolol CR/XL was well tolerated in all 3 renal function subgroups.ConclusionsRenal function as estimated by eGFR was a powerful predictor of death and hospitalizations from worsening HF. Metoprolol CR/XL was at least as effective in reducing death and hospitalizations for worsening HF in patients with eGFR < 45 as in those with eGFR > 60.     

Burden and Outcomes of Heart Failure Hospitalizations in Adults With Chronic Kidney Disease

BackgroundData on rates of heart failure (HF) hospitalizations, recurrent hospitalizations, and outcomes related to HF hospitalizations in chronic kidney disease (CKD) are limited.ObjectivesThis study examined rates of HF hospitalizations and re-hospitalizations within a large CKD population and evaluated the burden of HF hospitalizations with the risk of subsequent CKD progression and death.MethodsThe prospective CRIC (Chronic Renal Insufficiency Cohort) study measured the estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (ACR) at baseline. The crude rates and rate ratios of HF hospitalizations and 30-day HF re-hospitalizations were calculated using Poisson regression models. Cox regression was used to assess the association of the frequency of HF hospitalizations within the first 2 years of follow-up with risk of subsequent CKD progression and death.ResultsAmong 3,791 participants, the crude rate of HF admissions was 5.8 per 100 person-years (with higher rates of HF with preserved ejection fraction vs. HF with reduced ejection fraction). The adjusted rate of HF was higher with a lower eGFR (vs. eGFR >45 ml/min/1.73 m²); the rate ratios were 1.7 and 2.2 for eGFR 30 to 44 and <30 ml/min/1.73 m² (vs. >45 ml/min/1.73 m²), respectively. Similarly, the adjusted rates of HF hospitalization were significantly higher in those with higher urine ACR (vs. urine ACR <30 mg/g); the rate ratios were 1.9 and 2.6 for urine ACR 30 to 299 and ≥300 mg/g, respectively. Overall, 20.6% of participants had a subsequent HF re-admission within 30 days. HF hospitalization within 2 years of study entry was associated with greater adjusted risks for CKD progression (1 hospitalization: hazard ratio [HR]: 1.93; 95% confidence interval [CI]: 1.40 to 2.67; 2+ hospitalizations: HR: 2.14; 95% CI: 1.30 to 3.54) and all-cause death (1 hospitalization: HR: 2.20; 95% CI: 1.71 to 2.84; 2+ hospitalizations: HR: 3.06; 95% CI: 2.23 to 4.18).ConclusionsWithin a large U.S. CKD population, the rates of HF hospitalizations and re-hospitalization were high, with even higher rates across categories of lower eGFR and higher urine ACR. Patients with CKD hospitalized with HF had greater risks of CKD progression and death. HF prevention and treatment should be a public health priority to improve CKD outcomes.     

A Body Shape Index is positively associated with all-cause and cardiovascular disease mortality in the Chinese population with normal weight: A prospective cohort study

Background and aimA body shape index (ABSI) is a valuable predictor of mortality in the Western population, but similar evidence in the general Chinese population is limited. This study aims to evaluate the association between the ABSI and all-cause and cardiovascular disease (CVD) mortality in the Chinese population with normal weight.Methods and results9046 participants with normal BMI (18.5–24.9 kg/m²) from the China Hypertension Survey were enrolled. The baseline ABSI was calculated as waist circumference/(BMI^2/3height^1/2). Cox proportional hazards regression was performed to evaluate the association of the ABSI with all-cause and CVD mortality. Over an average follow-up of 5.4 years, 686 all-cause and 215 CVD deaths occurred. A 0.01-unit increment in the ABSI was associated with a 31% greater risk of all-cause mortality (hazard ratio [HR], 1.31; 95% CI: 1.12, 1.48) and CVD mortality (HR, 1.30; 95% CI: 1.08, 1.58). Compared with quartile 1 of the ABSI, the adjusted HRs of all-cause mortality for quartiles 2–4 were, respectively, 1.25 (95% CI: 0.98, 1.59), 1.28 (95% CI: 0.99, 1.67), and 1.54 (95% CI: 1.17, 2.03) (P_trend = 0.004), and those of CVD mortality for quartiles 2–4 were, respectively, 1.28 (95% CI: 0.88, 1.83), 1.42 (95% CI: 0.97, 2.08), and 1.45 (95% CI: 0.98, 2.170) (P_trend = 0.043). The dose–response analysis showed a linear positive association of the ABSI with all-cause (P_nonlinearity = 0.158) and CVD mortality (P_nonlinearity = 0.213).ConclusionThe ABSI was positively associated with all-cause and CVD mortality among the general Chinese population with normal BMI. The data suggest that the ABSI may be an effective tool for central fatness for mortality risk assessment.     

Right Ventricular–Pulmonary Arterial Coupling in Patients With HF Secondary MR: Analysis From the COAPT Trial

ObjectivesThe aim of this study was to determine the prognostic impact of right ventricular (RV)–pulmonary arterial (PA) coupling in patients with heart failure (HF) with severe secondary mitral regurgitation (SMR) enrolled in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial.BackgroundRV contractile function and PA pressures influence outcomes in patients with SMR, but the impact of RV-PA coupling in patients randomized to transcatheter edge-to-edge repair (TEER) vs guideline-directed medical therapy (GDMT) is unknown.MethodsRV-PA coupling was assessed by the ratio of RV free wall longitudinal strain derived from speckle-tracking echocardiography and noninvasively measured RV systolic pressure. Advanced RV-PA uncoupling was defined as RV free wall longitudinal strain/RV systolic pressure ≤0.5%/mm Hg. The primary endpoint was a composite of all-cause mortality or HF hospitalization at 24-month follow-up.ResultsA total of 372 patients underwent speckle-tracking echocardiography, and 70.2% had advanced RV-PA uncoupling. By multivariable analysis, advanced RV-PA uncoupling was strongly associated with an increased risk for the primary 24-month endpoint of death or HF hospitalization (HR: 1.87; 95% CI: 1.31-2.66; P = 0.0005). A similar association was present for all-cause mortality alone (HR: 2.57; 95% CI: 1.54-4.29; P = 0.0003). The impact of RV-PA uncoupling was consistent in patients randomized to TEER and GDMT alone. Compared with GDMT alone, the addition of TEER improved 2-year outcomes in patients with (48.0% vs 74.8%; HR: 0.51; 95% CI: 0.37-0.71) and those without (28.8% vs 47.8%; HR: 0.51; 95% CI: 0.27-0.97) advanced RV-PA uncoupling (P_interaction = 0.98).ConclusionsIn the COAPT trial, advanced RV dysfunction assessed by RV-PA uncoupling was a powerful predictor of 2-year adverse outcomes in patients with HF and SMR. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial]; NCT01626079)     

Impact of Transcatheter Mitral Valve Repair on Preprocedural and Postprocedural Hospitalization Rates

ObjectivesThe objective of this study was to determine the effect of transcatheter mitral valve repair (TMVr) on hospitalization rates by assessing pre- and postprocedural hospitalization patterns.BackgroundTMVr has emerged as the treatment of choice for selected patients with mitral regurgitation, but the impact of these procedures on hospital utilization remains unclear.MethodsAll patients who underwent TMVr in Ontario, Canada, between 2011 and 2017 were included in this observational study using population-based data. Hospitalization person-year rates were assessed in the years before and after TMVr and 4 predefined intervals: 1 to 30, 31 to 90, 91 to 182, and 183 to 365 days. Main outcomes of interest were all-cause and heart failure (HF) hospitalizations. Poisson regression models were used to compare incidence rates across all time periods.ResultsThe study cohort included 523 patients. In the year preceding TMVr, 66.2% of patients were hospitalized compared with 47.4% in the year following. There were stepwise increases in both all-cause and HF hospitalization rates in the periods preceding the index procedure, and all postprocedural periods had significantly lower hospitalization rates. The adjusted rate ratios for all-cause and HF-related hospitalization in the year after TMVr were 0.65 (95% CI: 0.56-0.76) and 0.38 (95% CI: 0.29-0.51), respectively. All time periods had significant reductions in all-cause and HF hospitalization in the adjusted analysis.ConclusionsIn this population-based study, significant reductions were observed in both all-cause and HF-related hospitalizations in all time periods after TMVr compared with the year prior. This suggests that TMVr has a sustained effect on hospitalization rates despite a high-risk population.     

The Association Between Socioeconomic Status,Sex, Race / Ethnicity and In-Hospital Mortality Among Patients Hospitalized for Heart Failure

BackgroundThe association between socioeconomic status (SES), sex, race / ethnicity and outcomes during hospitalization for heart failure (HF) has not previously been investigated.Methods and ResultsWe analyzed HF hospitalizations in the United States National Inpatient Sample between 2015 and 2017. Using a hierarchical, multivariable Poisson regression model to adjust for hospital- and patient-level factors, we assessed the association between SES, sex, and race / ethnicity and all-cause in-hospital mortality. We estimated the direct costs (USD) across SES groups. Among 4,287,478 HF hospitalizations, 40.8% were in high SES, 48.7% in female, and 70.0% in White patients. Relative to these comparators, low SES (homelessness or lowest quartile of median neighborhood income) (relative risk [RR] 1.02, 95% confidence interval [CI] 1.00–1.05) and male sex (RR 1.09, 95% CI 1.07–1.11) were associated with increased risk, whereas Black (RR 0.79, 95% CI 0.76–0.81) and Hispanic (RR 0.90, 95% CI 0.86–0.93) race / ethnicity were associated with a decreased risk of in-hospital mortality (5.1% of all hospitalizations). There were significant interactions between race / ethnicity and both, SES (P < .01) and sex (P = .04), such that racial/ethnic differences in outcome were more pronounced in low SES groups and in male patients. The median direct cost of admission was lower in low vs high SES groups ($9324.60 vs $10,940.40), female vs male patients ($9866.60 vs $10,217.10), and Black vs White patients ($9077.20 vs $10,019.80). The median costs increased with SES in all demographic groups primarily related to greater procedural utilization.ConclusionsSES, sex, and race / ethnicity were independently associated with in-hospital mortality during HF hospitalization, highlighting possible care disparities. Racial/ethnic differences in outcome were more pronounced in low SES groups and in male patients.     

Changes in uric Acid levels and allopurinol use in chronic heart failure: association with improved survival

ObjectiveUric acid (UA) levels are frequently increased in patients with heart failure (HF), and may be an indicator of a poor prognosis and an innovative target for treatment. We evaluated the effect of UA and allopurinol use on clinical outcome in patients with HF.Methods and ResultsWe evaluated patients with a diagnosis of HF at a Health Maintenance Organization (n = 6204). Patients were followed for cardiac-related hospitalizations and death. Mean UA levels were 6.5 ± 1.9 mg/dL. Median follow-up was 498 days. We divided patients into quartiles of serum UA; 22.6% (n = 1,568) were in the highest UA level quartile (>7.7 mg/dL). Cox regression analysis after adjustment for significant predictors including age, sex, ischemic heart disease, hypertension, atrial fibrillation, body mass index, hemoglobin, sodium, estimated glomerular filtration rate, urea levels, standard HF drug therapies, and allopurinol demonstrated that high UA levels (>7.7 mg/dL) were a predictor of increased mortality (hazard ratio [HR] 1.37, 95% confidence interval [CI] 1.17–1.60; P < .0001) and increased cardiac hospitalizations (HR 1.10, 95% CI 1.01–1.22; P < .05). An increase in UA levels during follow-up was also an independent predictor of mortality (HR 1.46, 95% CI 1.25–1.71; P < .00001) and cardiac hospitalizations (HR 1.15, 95% CI 1.06–1.23; P < .00001). Treatment with allopurinol was independently associated with improved survival (HR 0.79, 95% CI 0.64–0.98; P < .05). Echocardiographic data demonstrated a significant correlation between UA levels and E/A ratio, a marker of diastolic dysfunction.ConclusionsIncreased UA levels and an increase in UA during follow-up were independent predictors of increased morbidity and mortality. Treatment with allopurinol was associated with improved survival.     

Clinical Outcomes with β-Blockers for Myocardial Infarction: A Meta-analysis of Randomized Trials

BackgroundDebate exists about the efficacy of β-blockers in myocardial infarction and their required duration of usage in contemporary practice.MethodsWe conducted a MEDLINE/EMBASE/CENTRAL search for randomized trials evaluating β-blockers in myocardial infarction enrolling at least 100 patients. The primary outcome was all-cause mortality. Analysis was performed stratifying trials into reperfusion-era (> 50% undergoing reperfusion or receiving aspirin/statin) or pre-reperfusion-era trials.ResultsSixty trials with 102,003 patients satisfied the inclusion criteria. In the acute myocardial infarction trials, a significant interaction (P_interaction = .02) was noted such that β-blockers reduced mortality in the pre-reperfusion (incident rate ratio [IRR] 0.86; 95% confidence interval [CI], 0.79-0.94) but not in the reperfusion era (IRR 0.98; 95% CI, 0.92-1.05). In the pre-reperfusion era, β-blockers reduced cardiovascular mortality (IRR 0.87; 95% CI, 0.78-0.98), myocardial infarction (IRR 0.78; 95% CI, 0.62-0.97), and angina (IRR 0.88; 95% CI, 0.82-0.95), with no difference for other outcomes. In the reperfusion era, β-blockers reduced myocardial infarction (IRR 0.72; 95% CI, 0.62-0.83) (number needed to treat to benefit [NNTB] = 209) and angina (IRR 0.80; 95% CI, 0.65-0.98) (NNTB = 26) at the expense of increase in heart failure (IRR 1.10; 95% CI, 1.05-1.16) (number needed to treat to harm [NNTH] = 79), cardiogenic shock (IRR 1.29; 95% CI, 1.18-1.41) (NNTH = 90), and drug discontinuation (IRR 1.64; 95% CI, 1.55-1.73), with no benefit for other outcomes. Benefits for recurrent myocardial infarction and angina in the reperfusion era appeared to be short term (30 days).ConclusionsIn contemporary practice of treatment of myocardial infarction, β-blockers have no mortality benefit but reduce recurrent myocardial infarction and angina (short-term) at the expense of increase in heart failure, cardiogenic shock, and drug discontinuation. The guideline authors should reconsider the strength of recommendations for β-blockers post myocardial infarction.     

Pulmonary Vascular Resistance Is Associated With Brachial-Ankle Pulse-Wave Velocity and Adverse Clinical Outcomes in Patients With Heart Failure With Preserved Ejection Fraction

BackgroundThe precise mechanisms underlying the high prevalence of pulmonary hypertension (PH) with increased pulmonary vascular resistance (PVR) in heart failure with preserved ejection fraction (HFpEF) remain largely unknown. Measurements of brachial-ankle pulse wave velocity (baPWV) have been shown to be useful for risk assessment in HF patients. Thus, this study sought to define the association of PVR with baPWV and clinical outcomes in HFpEF.Methods and ResultsPatients with HFpEF (n = 198) had measurements of baPWV and PVR by right heart catheterization, and were prospectively followed-up for <96 months or until the occurrence of a composite of all-cause death, hospitalization with worsening HF, and nonfatal acute coronary syndrome.ResultsMultivariate logistic analysis showed that baPWV was independently associated with PH with increased PVR (P < .001). During the follow-up period, 46 clinical events occurred. Multivariate Cox proportional hazards analysis showed that PH with increased PVR was a significant predictor of adverse outcomes after adjustment for conventional risk factors (HR 1.96, 95% CI 1.03–3.76, P = .04).ConclusionsPH with increased PVR was associated with increased baPWV and adverse clinical outcomes in HFpEF. Thus, increased arterial stiffness may contribute to increased risk predictability of PVR for patients with HFpEF.     

Prognostic Impact of Worsening Renal Function in Hospitalized Heart Failure Patients With Preserved Ejection Fraction: A Report From the JASPER Registry

BackgroundThe characteristics and prognostic impact of persistent worsening renal function (WRF; defined as an increase in serum creatinine of >0.3 mg/dL during hospitalization) on heart failure with preserved ejection fraction have not yet been fully examined.Methods and ResultsThis was a post hoc analysis of the Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry. We divided 523 patients with heart failure with preserved ejection fraction: the WRF group (n = 92 [17.6%]) and the non-WRF group (n = 431 [82.4%]). The WRF group showed a higher systolic blood pressure on admission and a higher prevalence of atherosclerotic diseases, respectively. Logistic regression analysis revealed that systolic blood pressure and loop diuretics were associated with WRF development (P < .05). The Kaplan-Meier analysis (median, 732 days) showed a higher all-cause death in the WRF group, as well as a higher composite end point of all-cause death or rehospitalization for HF (log-rank P < .001). The Cox proportional hazard analysis revealed WRF to be a predictor of both all-cause death (hazard ratio, 2.725; 95% confidence interval, 1.709–4.344; P < .001) and the composite end point (hazard ratio, 2.083; 95% confidence interval, 1.488–2.914; P < .001).ConclusionsPersistent WRF was associated with systolic blood pressure, atherosclerotic diseases, diuretics, and poor postdischarge prognosis in patients with heart failure with preserved ejection fraction.     

Associations of vitamin B6 turnover rate with the risk of cardiovascular and all-cause mortality in hypertensive adults

Background and aimThis study was to assess the association between vitamin B6 turnover rate and mortality in hypertensive adults.Methods and resultsVitamin B6 status including serum pyridoxal-5′-phosphate (PLP) levels, serum 4-pyridoxal acid (4-PA) levels, and vitamin B6 turnover rate (4-PA/PLP) were obtained from the 2005–2010 National Health and Nutrition Examination Survey (NHANES) dataset of hypertensive adults with follow-up through December 30, 2019. Using Cox proportional risk regression models, Hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed for PLP, 4-PA and 4-PA/PLP quartiles in relation to cardiovascular and all-cause mortality. A total of 5434 participants were included in this study (mean age, 58.48 years; 50.4% men), and the median 4-PA/PLP was 0.75. The median follow-up time was 11.0 years, with 375 and 1387 cardiovascular and all-cause deaths, respectively. In multivariate COX regression models, PLP was negatively associated with cardiovascular mortality (HR [95% CI] quartile 4 vs. 1: 0.66 [0.47–0.94], P_trend = 0.03) and 4-PA/PLP was positively associated with cardiovascular mortality (HR [95% CI] quartile 4 vs.1: 1.80 [1.21–2.67], P_trend = 0.01). Similarly, the higher the quartile of PLP, the lower the risk of all-cause mortality (HR [95% CI] quartile 4 vs. 1: 0.67 [0.56–0.80], P_trend < 0.01). The higher the quartile of 4-PA and 4-PA/PLP, the higher the risk of all-cause mortality (HR [95% CI] quartile 4 vs. 1: 1.22 [1.01–1.48], P_trend < 0.01; and 2.09 [1.71–2.55], P_trend < 0.01).ConclusionThe findings suggested that higher vitamin B6 turnover rate was associated with an increased risk of cardiovascular and all-cause mortality in hypertensive adults.