#Probenecid Improves Cardiac Function in Patients With #Heart #Failure With Reduced Ejection Fraction In Vivo and Cardiomyocyte Calcium Sensitivity In Vitro

http://jaha.ahajournals.org/content/7/2/e007148.long


The clinical trial recruited stable outpatients with heart failure with reduced ejection fraction randomized in a single‐center, double‐blind, crossover design. Clinical data were collected including a dyspnea assessment, physical examination, ECG, echocardiogram to assess systolic and diastolic function, a 6‐minute walk test, and laboratory studies. In vitro force generation studies were performed on cardiomyocytes isolated from murine tissue exposed to probenecid or control treatments. The clinical trial recruited 20 subjects (mean age 57 years, mean baseline fractional shortening of 13.6±1.0%). Probenecid therapy increased fractional shortening by 2.1±1.0% compared with placebo −1.7±1.0% (P=0.007). Additionally, probenecid improved diastolic function compared with placebo by decreasing the E/E′ by −2.95±1.21 versus 1.32±1.21 in comparison to placebo (P=0.03). In vitro probenecid increased myofilament force generation (92.36 versus 80.82 mN/mm2, P<0.05) and calcium sensitivity (pCa 5.67 versus 5.60, P<0.01) compared with control.


Conclusions Probenecid improves cardiac function with minimal effects on symptomatology and no significant adverse effects after 1 week in patients with heart failure with reduced ejection fraction and increases force development and calcium sensitivity at the cardiomyocyte level.

Lack of Association Between Heart #Failure and Incident #Cancer

http://www.onlinejacc.org/content/71/14/1501


Among 28,341 Physicians’ Health Study participants, 1,420 developed HF. A total of 7,363 cancers developed during a median follow-up time of 19.9 years (25th to 75th percentile: 11.0 to 26.8 years). HF was not associated with cancer incidence in crude (hazard ratio: 0.92; 95% confidence interval: 0.80 to 1.08) or multivariable-adjusted analysis (hazard ratio: 1.05; 95% confidence interval: 0.86 to 1.29). No association was found between HF and site-specific cancer incidence or cancer-specific mortality after multivariable adjustment. Results were similar when using the landmark method at all landmark ages.

Conclusions HF is not associated with an increased risk of cancer among male physicians.

Effects of #Sacubitril/Valsartan on Physical and Social Activity Limitations in Patients With Heart #Failure
A Secondary Analysis of the PARADIGM-HF Trial

https://jamanetwork.com/journals/jamacardiology/fullarticle/2677630


At baseline, 7618 of 8399 patients (90.7%) (mean SD age, 64 11 years; 5987 78.6% male and 1631 21.4% female) completed the initial KCCQ assessment. Patients reported the greatest limitations at baseline in jogging and sexual relationships. Patients receiving sacubitril/valsartan had significantly better adjusted change scores in most physical and social activities at 8 months and during 36 months compared with those receiving enalapril. The largest improvement over enalapril was in household chores (adjusted change score difference, 2.35; 95% CI, 1.19-3.50; P < .001) and sexual relationships (adjusted change score difference, 2.72; 95% CI, 0.97-4.46; P = .002); both persisted through 36 months (overall change score difference, 1.69 95% CI, 0.78-2.60, P < .001; and 2.36 95% CI, 1.01-3.71, P = .001, respectively).

Conclusions and Relevance In patients with heart failure with reduced ejection fraction, sacubitril/valsartan significantly improved nearly all KCCQ physical and social activities compared with enalapril, with the largest responses in household chores and sexual relationships. In addition to reduced likelihood of cardiovascular death, all-cause mortality, and heart failure hospitalization, sacubitril/valsartan may improve limitations in common activities in these patients

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The Intensive Care Unit (ICU) course and outcome in Acute-on-chronic #liver #failure are comparable to other populations

https://www.journal-of-hepatology.eu/article/S0168-8278(18)32043-9/fulltext?mobileUi=0


The outcome of ACLF, when compared to septic or medical ICU patients, matched for baseline parameters of illness severity, was similar regarding length of ICU stay, development of new infections, organ failure and septic shock. ICU, hospital and 90-day mortality were similar between the groups. C-reactive protein and platelet levels were lower in ACLF throughout the first week. Cytokines on day 1 including IL-10, IL-1β, IL-6, and IL-8 were similarly elevated in ACLF and septic ICU patients. TNF-α levels were however higher in ACLF.

Conclusion
ACLF patients admitted to the ICU showed comparable clinical and ICU outcomes compared to ICU patients without chronic liver disease with similar baseline severity of illness characteristics. This suggests that ICU admission criteria should not be different in ACLF compared to other populations.

Association of Ambulatory Blood #Pressure with All-Cause and Cardiovascular Mortality in Hemodialysis Patients: Effects of Heart #Failure and Atrial #Fibrillation

http://m.jasn.asnjournals.org/content/early/2018/07/24/ASN.2018010086.short?rss=1


During the mean 37.6-month follow-up, 115 patients died (47 from a cardiovascular cause). SBP and PP showed a U-shaped association with all-cause and cardiovascular mortality in the cohort. In linear subgroup analysis, SBP and PP were independent risk predictors and showed a significant inverse relationship to all-cause and cardiovascular mortality in patients with atrial fibrillation or heart failure. In patients without these conditions, these associations were in the opposite direction. SBP and PP were significant independent risk predictors for cardiovascular mortality; PP was a significant independent risk predictor for all-cause mortality.

Conclusions This study provides evidence for the U-shaped association between peripheral ambulatory SBP or PP and mortality in patients on hemodialysis. Furthermore, it suggests that underlying cardiac disease can explain the opposite direction of associations.

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Transcatheter #Mitral-Valve Repair in Patients with Heart #Failure

https://www.nejm.org/doi/full/10.1056/NEJMoa1806640

Of the 614 patients who were enrolled in the trial, 302 were assigned to the device group and 312 to the control group. The annualized rate of all hospitalizations for heart failure within 24 months was 35.8% per patient-year in the device group as compared with 67.9% per patient-year in the control group (hazard ratio, 0.53; 95% confidence interval CI, 0.40 to 0.70; P<0.001). The rate of freedom from device-related complications at 12 months was 96.6% (lower 95% confidence limit, 94.8%; P<0.001 for comparison with the performance goal). Death from any cause within 24 months occurred in 29.1% of the patients in the device group as compared with 46.1% in the control group (hazard ratio, 0.62; 95% CI, 0.46 to 0.82; P<0.001).

CONCLUSIONS
Among patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy, transcatheter mitral-valve repair resulted in a lower rate of hospitalization for heart failure and lower all-cause mortality within 24 months of follow-up than medical therapy alone. The rate of freedom from device-related complications exceeded a prespecified safety threshold.

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Association of Unrecognized Myocardial Infarction With Long-term Outcomes in Community-Dwelling Older Adults

https://jamanetwork.com/journals/jamacardiology/fullarticle/2705678

Of 935 participants, 452 (48.3%) were men; the mean (SD) age of participants with no MI, UMI, and RMI was 75.6 (5.3) years, 76.8 (5.2) years, and 76.8 (4.7) years, respectively. At 3 years, UMI and no #MI mortality rates were similar (3%) and lower than RMI rates (9%). At 5 years, UMI mortality rates (13%) increased and were higher than no MI rates (8%) but still lower than RMI rates (19%). By 10 years, UMI and RMI mortality rates (49% and 51%, respectively) were not statistically different; both were significantly higher than no MI (30%) (P < .001). After adjusting for age, sex, and diabetes, UMI by CMR had an increased risk of death (hazard ratio [HR], 1.61; 95% CI, 1.27-2.04), MACE (HR, 1.56; 95% CI, 1.26-1.93), MI (HR, 2.09; 95% CI, 1.45-3.03), and heart failure (HR, 1.52; 95% CI, 1.09-2.14) compared with no MI and statistically nondifferent risk of death (HR, 0.99; 95% CI, 0.71-1.38) and MACE (HR, 1.23; 95% CI, 0.91-1.66) vs RMI.

Conclusions and Relevance In this study, all-cause mortality of UMI was higher than no MI, but within 10 years from baseline evaluation was equivalent with RMI. Unrecognized MI was also associated with an elevated risk of nonfatal MI and heart #failure. Whether secondary prevention can alter the prognosis of UMI will require prospective testing.

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Reduced #Salt Intake for Heart #Failure
A Systematic Review

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2712563

Of 2655 retrieved references, 9 studies involving 479 unique participants were included in the analysis. None of the studies included more than 100 participants. The risks of bias in the 9 studies were variable. None of the included studies provided sufficient data on the primary outcomes of interest. For the secondary outcomes of interest, 2 outpatient-based studies reported that NYHA functional class was not improved by restriction of salt intake, whereas 2 studies reported significant improvements in NYHA functional class.

Conclusions and Relevance Limited evidence of clinical improvement was available among outpatients who reduced dietary salt intake, and evidence was inconclusive for inpatients. Overall, a paucity of robust high-quality evidence to support or refute current guidance was available. This review suggests that well-designed, adequately powered studies are needed to reduce uncertainty about the use of this intervention.

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Effect of early physician follow-up on mortality and subsequent hospital admissions after #emergency care for heart #failure: a retrospective cohort study

http://www.cmaj.ca/content/190/50/E1468

Of 34 519 patients, 16 274 (47.1%) obtained follow-up care within 7 days and 28 846 (83.6%) within 30 days. Compared with follow-up between day 8 and 30, patients with follow-up care within 7 days had a lower rate of mortality over 1 year (hazard ratio [HR] 0.92; 95% confidence interval [CI] 0.87–0.97), and a reduced rate of admission to hospital over 90 days (HR 0.87, 95% CI 0.80–0.94) and 1 year (HR 0.92; 95% CI 0.87–0.97); the mortality rate over 90 days in this group trended to a lower rate (HR 0.90, 95% CI 0.10–1.00). Follow-up care within 30 days, compared with patients without 30-day follow-up, was associated with a reduction in 1-year mortality (HR 0.89, 95% CI 0.82–0.97) but not admission to hospital (HR 1.02, 95% CI 0.94–1.10). In this group, there was a trend toward an increase in 90-day admission to hospital (HR 1.14, 95% CI 1.00–1.29).

INTERPRETATION: Follow-up care within 7 days of discharge from the emergency department was associated with lower rates of long-term mortality, as well as subsequent hospital admissions, and a trend to lower short-term mortality rates. Timely access to longitudinal care for patients with heart failure who are discharged from the emergency setting should be prioritized.

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External Validation of the #MEESSI Acute Heart #Failure Risk Score: A Cohort Study

https://annals.org/aim/article-abstract/2723394/external-validation-meessi-acute-heart-failure-risk-score-cohort-study

The MEESSI-AHF (Multiple Estimation of risk based on the Emergency department Spanish Score In patients with AHF) score was developed to predict 30-day mortality in patients presenting with acute heart failure (AHF) to emergency departments (EDs) in Spain.

The score predicted 30-day mortality with excellent discrimination (c-statistic, 0.80). Assessment of cumulative mortality showed a steep gradient in 30-day mortality over 6 predefined risk groups (0 patients in the lowest-risk group vs. 35 28.5% in the highest-risk group). Risk was overestimated in the high-risk groups, resulting in a Hosmer–Lemeshow P value of 0.022. However, after adjustment of the intercept, the model showed good concordance between predicted risks and observed outcomes (P = 0.23). Findings were confirmed in sensitivity analyses that used multiple imputation for missing values in the overall cohort of 1572 patients.

External validation of the MEESSI-AHF risk score showed excellent discrimination. Recalibration may be needed when the score is introduced to new populations.

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#Systolic Blood Pressure and Outcomes in Patients With Heart #Failure With Reduced Ejection Fraction

http://www.onlinejacc.org/content/73/24/3054

National guidelines recommend that systolic blood pressure (SBP) in patients with heart failure with reduced ejection fraction (HFrEF) and hypertension be maintained below 130 mm Hg.

Thirty-day all-cause mortality occurred in 7% and 4% of matched patients with SBP <130 mm Hg versus ≥130 mm Hg, respectively (hazard ratio HR: 1.76; 95% confidence interval CI: 1.24 to 2.48; p = 0.001). HRs (95% CIs) for all-cause mortality, all-cause readmission, and HF readmission at 1 year, associated with SBP <130 mm Hg, were 1.32 (1.15 to 1.53; p < 0.001), 1.11 (1.01 to 1.23; p = 0.030), and 1.24 (1.09 to 1.42; p = 0.001), respectively. HRs (95% CIs) for 30-day and 1-year all-cause mortality associated with SBP 110 to 129 mm Hg (vs. ≥130 mm Hg) were 1.50 (1.03 to 2.19; p = 0.035), and 1.19 (1.02 to 1.39; p = 0.029), respectively.

Conclusions Among hospitalized older patients with HFrEF, SBP <130 mm Hg is associated with poor outcomes. This association persisted when the analyses were repeated after excluding patients with SBP <110 mm Hg. There is an urgent need for randomized controlled trials to evaluate optimal SBP reduction goals in patients with HFrEF.

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Association of #Carpal Tunnel Syndrome With #Amyloidosis, Heart #Failure, and Adverse Cardiovascular Outcomes

http://www.onlinejacc.org/content/74/1/15

Recent studies have suggested that transthyretin amyloidosis (ATTR) is a more common cause of heart failure (HF) than previously appreciated, and novel treatments for amyloidosis are emerging. About one-half of patients with ATTR cardiac amyloidosis have a history of carpal tunnel syndrome (CTS).

As expected, CTS was associated with a future diagnosis of amyloidosis (hazard ratio: 12.12 95% confidence interval: 4.37 to 33.60). CTS was associated with a higher incidence of HF, and this held true in the adjusted analysis yielding a hazard ratio of 1.54 (95% confidence interval: 1.45 to 1.64). No significant interaction with sex was found (p = 0.5). Risk of other adverse outcomes was also associated with CTS (p < 0.0001 for atrial fibrillation, atrioventricular heart block, and pacemaker implantation).

Conclusions Patients who undergo surgical treatment for CTS are associated with a higher risk of amyloidosis and HF relative to matched control subjects from the general population. Other cardiovascular outcomes were also increased with CTS.

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Improved #oral hygiene care is associated with decreased risk of occurrence for atrial #fibrillation and heart #failure: A nationwide population-based cohort study

Poor oral hygiene can provoke transient bacteremia and systemic inflammation, a mediator of atrial fibrillation and heart failure..

.. In multivariate analysis after adjusting age, sex, socioeconomic status, regular exercise, alcohol consumption, body mass index, hypertension, diabetes, dyslipidemia, current smoking, renal disease, history of cancer, systolic blood pressure, blood and urine laboratory findings, frequent tooth brushing (≥3 times/day) was significantly associated with attenuated risk of atrial fibrillation (hazard ratio: 0.90, 95% confidence interval (0.83–0.98)) and heart failure (0.88, (0.82–0.94)). Professional dental cleaning was negatively (0.93, (0.88–0.99)), while number of missing teeth ≥22 was positively (1.32, (1.11–1.56)) associated with risk of heart failure.

Conclusion
Improved oral hygiene care was associated with decreased risk of atrial fibrillation and heart failure. Healthier oral hygiene by frequent tooth brushing and professional dental cleaning may reduce risk of atrial fibrillation and heart failure

https://journals.sagepub.com/doi/10.1177/2047487319886018

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Risk Factors for Heart #Failure in the Community: Differences by Age and Ejection #Fraction

..the comorbidities with the largest attributable risk of heart failure were arrhythmia (48.7%), hypertension (28.4%), and coronary artery disease (33.9%); together these explained 73.0% of heart failure. Similar associations were observed for patients with reduced and preserved ejection fraction, with the exception of hypertension. The risk of heart failure attributable to hypertension was 2-fold higher in patients with heart failure with preserved ejection fraction (38.7%) than in patients with heart failure with reduced ejection fraction (17.8%). Hypertension, coronary artery disease, arrhythmia, and diabetes were more strongly associated with heart failure in younger (≤75 years) compared to older (>75 years) persons.

Conclusions
Patients with heart failure have a higher prevalence of many chronic conditions than controls. Similar associations were observed in patients with reduced and preserved ejection fraction, with the exception of hypertension, which was more strongly associated with heart failure with preserved ejection fraction.

Finally, some cardiometabolic risk factors were more strongly associated with heart failure in younger persons, highlighting the importance of optimizing prevention and treatment of risk factors and, in particular, cardiometabolic risk factors.

https://bit.ly/35lctEd

Temporal Changes in Resting #Heart Rate, Left Ventricular Dysfunction, Heart #Failure and Cardiovascular Disease: CARDIA Study

..Higher alcohol consumption (β=0.03, p<0.001), lower physical activity (β=0.002,p=001), smoking (β=1.58, p<0.001), men (p<0.001), African-Americans (p<0.001), impaired left ventricular relaxation (e´,β=-0.13, p=0.002), and worse diastolic function (E/e´,β=0.1, p=0.01) were associated with longitudinal increases in resting heart rate. We observed 268 cardiovascular disease and 74 heart failure events over a median of 26 years. In Cox models, baseline and temporal changes in resting heart rate were associated with higher risk of heart failure (hazard ratio (HR)=1.37 95% confidence interval (CI) [1.05-1.79] and HR=1.38 95%CI [1.02-1.86]) and a higher risk cardiovascular disease (HR=1.23 95%CI [1.07-1.42] and HR=1.23 95%CI [1.05-1.44]).

Conclusions

Baseline and temporal changes in resting heart rate in young adults were associated with incident heart failure and cardiovascular disease by mid-life. Contributory factors were associations between temporal increases in resting heart rate and early adult risk factors and subsequent cardiac dysfunction.

https://bit.ly/2tZIXXY

#Hypocalcaemia predicts 12‐month re‐hospitalization in heart #failure
https://2medical.news/2020/05/28/hypocalcaemia-predicts-12%E2%80%90month-re%E2%80%90hospitalization-in-heart-failure/

Potential pathophysiology of heart failure with preserved ejection fraction (HFpEF) has not been fully explored. The aim of the study was to reveal the association of serum calcium concentration at baseline with 12‐month clinical outcome in the disease.. ..Multivariate COX regression analysis revealed that baseline hypocalcaemia was associated with the increased risk of cardiac re‐hospitalization and death during the follow‐up period (HR: 2.10, 95% CI: …

#Anaemia, iron status, and gender predict the outcome in patients with chronic heart #failure
https://2medical.news/2020/06/02/anaemia-iron-status-and-gender-predict-the-outcome-in-patients-with-chronic-heart-failure/

Anaemia and iron deficiency (ID) are frequently found in patients with chronic heart failure (CHF) and associated with adverse outcome. However, it is unclear whether absolute [transferrin saturation (TSAT) 100 μg/L) with and without anaemia had similar or different consequences for such patients Within this retrospective cohort study, 2223 patients (1601 men and 622 …

Predictors of Mortality in Patients with Chronic Heart #Failure: Is #Hyponatremia a Useful Clinical Biomarker?
https://2medical.news/2020/07/26/predictors-of-mortality-in-patients-with-chronic-heart-failure-is-hyponatremia-a-useful-clinical-biomarker/

Chronic heart failure (CHF) is a global health burden. Despite advances in treatment, there remain well-recognised morbidity and mortality. Risk stratification requires the identification and validation of biomarkers, old and new. Hyponatremia has re-emerged as a prognostic marker in CHF patients.. ..Mean age of patients was 60.61 ± 12.63 (SD) years; 65.1% were males, and type 2 diabetes mellitus (DM) was present in 71%. Baseline …

Association of #Sedentary Time and Incident Heart #Failure Hospitalization in Postmenopausal Women
https://2medical.news/2020/12/05/association-of-sedentary-time-and-incident-heart-failure-hospitalization-in-postmenopausal-women/

Background: The 2018 US Physical Activity Guidelines recommend reducing sedentary behavior (SB) for cardiovascular health. SB’s role in heart failure (HF) is unclear. Methods: We studied 80 982 women in the Women’s Health Initiative Observational Study, aged 50 to 79 years, who were without known HF and reported ability to walk ≥1 block unassisted at baseline. Mean follow-up was 9 years for physician-adjudicated incident HF …