Left ventricular ejection fraction (LVEF) has been the central parameter used for diagnosis and management in patients with heart failure. A good predictor of adverse outcomes in heart failure when ...below ∼45%, LVEF is less useful as a marker of risk as it approaches normal. As a measure of cardiac function, ejection fraction has several important limitations. Calculated as the stroke volume divided by end-diastolic volume, the estimation of ejection fraction is generally based on geometric assumptions that allow for assessment of volumes based on linear or two-dimensional measurements. Left ventricular ejection fraction is both preload- and afterload-dependent, can change substantially based on loading conditions, is only moderately reproducible, and represents only a single measure of risk in patients with heart failure. Moreover, the relationship between ejection fraction and risk in patients with heart failure is modified by factors such as hypertension, diabetes, and renal function. A more complete evaluation and understanding of left ventricular function in patients with heart failure requires a more comprehensive assessment: we conceptualize an integrative approach that incorporates measures of left and right ventricular function, left ventricular geometry, left atrial size, and valvular function, as well as non-imaging factors (such as clinical parameters and biomarkers), providing a comprehensive and accurate prediction of risk in heart failure.
Objectives This study sought to determine the frequency and magnitude of impaired systolic deformation in heart failure with preserved ejection fraction (HFpEF). Background Although diastolic ...dysfunction is widely considered a key pathophysiologic mediator of HFpEF, the prevalence of concomitant systolic dysfunction has not been clearly defined. Methods We assessed myocardial systolic and diastolic function in 219 HFpEF patients from a contemporary HFpEF clinical trial. Myocardial deformation was assessed using a vendor-independent 2-dimensional speckle-tracking software. The frequency and severity of impaired deformation was assessed in HFpEF, and compared to 50 normal controls free of cardiovascular disease and to 44 age- and sex-matched hypertensive patients with diastolic dysfunction (hypertensive heart disease) but no HF. Among HFpEF patients, clinical, echocardiographic, and biomarker correlates of left ventricular strain were determined. Results The HFpEF patients had preserved left ventricular ejection fraction and evidence of diastolic dysfunction. Compared to both normal controls and hypertensive heart disease patients, the HFpEF patients demonstrated significantly lower longitudinal strain (LS) (−20.0 ± 2.1 and −17.07 ± 2.04 vs. −14.6 ± 3.3, respectively, p < 0.0001 for both) and circumferential strain (CS) (−27.1 ± 3.1 and −30.1 ± 3.5 vs. −22.9 ± 5.9, respectively; p < 0.0001 for both). In HFpEF, both LS and CS were related to LVEF (LS, R = −0.46; p < 0.0001; CS, R = −0.51; p < 0.0001) but not to standard echocardiographic measures of diastolic function (E' or E/E'). Lower LS was modestly associated with higher NT-proBNP, even after adjustment for 10 baseline covariates including LVEF, measures of diastolic function, and LV filling pressure (multivariable adjusted p = 0.001). Conclusions Strain imaging detects impaired systolic function despite preserved global LVEF in HFpEF that may contribute to the pathophysiology of the HFpEF syndrome. (LCZ696 Compared to Valsartan in Patients With Chronic Heart Failure and Preserved Left-ventricular Ejection Fraction; NCT00887588 )
Severe COVID-19 Is a Microvascular Disease Lowenstein, Charles J; Solomon, Scott D
Circulation (New York, N.Y.),
2020-October-27, Letnik:
142, Številka:
17
Journal Article
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19) has reached a pandemic level. Coronaviruses are known to affect the cardiovascular ...system. We review the basics of coronaviruses, with a focus on COVID-19, along with their effects on the cardiovascular system.
Coronavirus disease 2019 can cause a viral pneumonia with additional extrapulmonary manifestations and complications. A large proportion of patients have underlying cardiovascular disease and/or cardiac risk factors. Factors associated with mortality include male sex, advanced age, and presence of comorbidities including hypertension, diabetes mellitus, cardiovascular diseases, and cerebrovascular diseases. Acute cardiac injury determined by elevated high-sensitivity troponin levels is commonly observed in severe cases and is strongly associated with mortality. Acute respiratory distress syndrome is also strongly associated with mortality.
Coronavirus disease 2019 is associated with a high inflammatory burden that can induce vascular inflammation, myocarditis, and cardiac arrhythmias. Extensive efforts are underway to find specific vaccines and antivirals against SARS-CoV-2. Meanwhile, cardiovascular risk factors and conditions should be judiciously controlled per evidence-based guidelines.
Heart failure drug treatment Rossignol, Patrick; Hernandez, Adrian F; Solomon, Scott D ...
The Lancet (British edition),
03/2019, Letnik:
393, Številka:
10175
Journal Article
Recenzirano
Odprti dostop
Heart failure is the most common cardiovascular reason for hospital admission for people older than 60 years of age. Few areas in medicine have progressed as remarkably as heart failure treatment ...over the past three decades. However, progress has been consistent only for chronic heart failure with reduced ejection fraction. In acutely decompensated heart failure and heart failure with preserved ejection fraction, none of the treatments tested to date have been definitively proven to improve survival. Delaying or preventing heart failure has become increasingly important in patients who are prone to heart failure. The prevention of worsening chronic heart failure and hospitalisations for acute decompensation is also of great importance. The objective of this Series paper is to provide a concise and practical summary of the available drug treatments for heart failure. We support the implementation of the international guidelines. We offer views on the basis of our personal experience in research areas that have insufficient evidence. The best possible evidence-based drug treatment (including inhibitors of the renin–angiotensin–aldosterone system and β blockers) is useful only when optimally implemented. However, implementation might be challenging. We believe that disease management programmes can be helpful in providing a multidisciplinary, holistic approach to the delivery of optimal medical care.
Low carbohydrate diets, which restrict carbohydrate in favour of increased protein or fat intake, or both, are a popular weight-loss strategy. However, the long-term effect of carbohydrate ...restriction on mortality is controversial and could depend on whether dietary carbohydrate is replaced by plant-based or animal-based fat and protein. We aimed to investigate the association between carbohydrate intake and mortality.
We studied 15 428 adults aged 45–64 years, in four US communities, who completed a dietary questionnaire at enrolment in the Atherosclerosis Risk in Communities (ARIC) study (between 1987 and 1989), and who did not report extreme caloric intake (<600 kcal or >4200 kcal per day for men and <500 kcal or >3600 kcal per day for women). The primary outcome was all-cause mortality. We investigated the association between the percentage of energy from carbohydrate intake and all-cause mortality, accounting for possible non-linear relationships in this cohort. We further examined this association, combining ARIC data with data for carbohydrate intake reported from seven multinational prospective studies in a meta-analysis. Finally, we assessed whether the substitution of animal or plant sources of fat and protein for carbohydrate affected mortality.
During a median follow-up of 25 years there were 6283 deaths in the ARIC cohort, and there were 40 181 deaths across all cohort studies. In the ARIC cohort, after multivariable adjustment, there was a U-shaped association between the percentage of energy consumed from carbohydrate (mean 48·9%, SD 9·4) and mortality: a percentage of 50–55% energy from carbohydrate was associated with the lowest risk of mortality. In the meta-analysis of all cohorts (432 179 participants), both low carbohydrate consumption (<40%) and high carbohydrate consumption (>70%) conferred greater mortality risk than did moderate intake, which was consistent with a U-shaped association (pooled hazard ratio 1·20, 95% CI 1·09–1·32 for low carbohydrate consumption; 1·23, 1·11–1·36 for high carbohydrate consumption). However, results varied by the source of macronutrients: mortality increased when carbohydrates were exchanged for animal-derived fat or protein (1·18, 1·08–1·29) and mortality decreased when the substitutions were plant-based (0·82, 0·78–0·87).
Both high and low percentages of carbohydrate diets were associated with increased mortality, with minimal risk observed at 50–55% carbohydrate intake. Low carbohydrate dietary patterns favouring animal-derived protein and fat sources, from sources such as lamb, beef, pork, and chicken, were associated with higher mortality, whereas those that favoured plant-derived protein and fat intake, from sources such as vegetables, nuts, peanut butter, and whole-grain breads, were associated with lower mortality, suggesting that the source of food notably modifies the association between carbohydrate intake and mortality.
National Institutes of Health.
Certain individuals, when infected by SARS-CoV-2, tend to develop the more severe forms of Covid-19 illness for reasons that remain unclear.
To determine the demographic and clinical characteristics ...associated with increased severity of Covid-19 infection.
Retrospective observational study. We curated data from the electronic health record, and used multivariable logistic regression to examine the association of pre-existing traits with a Covid-19 illness severity defined by level of required care: need for hospital admission, need for intensive care, and need for intubation.
A large, multihospital healthcare system in Southern California.
All patients with confirmed Covid-19 infection (N = 442).
Of all patients studied, 48% required hospitalization, 17% required intensive care, and 12% required intubation. In multivariable-adjusted analyses, patients requiring a higher levels of care were more likely to be older (OR 1.5 per 10 years, P<0.001), male (OR 2.0, P = 0.001), African American (OR 2.1, P = 0.011), obese (OR 2.0, P = 0.021), with diabetes mellitus (OR 1.8, P = 0.037), and with a higher comorbidity index (OR 1.8 per SD, P<0.001). Several clinical associations were more pronounced in younger compared to older patients (Pinteraction<0.05). Of all hospitalized patients, males required higher levels of care (OR 2.5, P = 0.003) irrespective of age, race, or morbidity profile.
In our healthcare system, greater Covid-19 illness severity is seen in patients who are older, male, African American, obese, with diabetes, and with greater overall comorbidity burden. Certain comorbidities paradoxically augment risk to a greater extent in younger patients. In hospitalized patients, male sex is the main determinant of needing more intensive care. Further investigation is needed to understand the mechanisms underlying these findings.
Abstract Background Natriuretic peptides (NP) have prognostic value in heart failure (HF), although the clinical importance of changes in NP from baseline is unclear. Objectives The authors assessed ...whether a reduction in N-terminal pro–B-type NP (NT-proBNP) was associated with a decrease in HF hospitalization and cardiovascular mortality (primary endpoint) in patients with HF and reduced ejection fraction, whether treatment with sacubitril/valsartan reduced NT-proBNP below specific partition values more than enalapril, and whether the relationship between changes in NT-proBNP and changes in the primary endpoint were dependent on assigned treatment. Methods In PARADIGM-HF (Prospective Comparison of ARNI Angiotensin Receptor–Neprilysin Inhibitor with ACEI Angiotensin-Converting–Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial), baseline NT-proBNP was measured in 2,080 patients; 1,292 had baseline values >1,000 pg/ml and were reassessed at 1 and 8 months. We related change in NT-proBNP to outcomes. Results One month after randomization, 24% of the baseline NT-proBNP levels >1,000 pg/ml had fallen to ≤1,000 pg/ml. Risk of the primary endpoint was 59% lower in patients with a fall in NT-proBNP to ≤1,000 pg/ml than in those without such a fall. In sacubitril/valsartan-treated patients, median NT-proBNP was significantly lower 1 month after randomization than in enalapril-treated patients, and it fell to ≤1,000 pg/ml in 31% versus 17% of patients treated with sacubitril/valsartan and enalapril, respectively. There was no significant interaction between treatment and the relationship between change in NT-proBNP and the subsequent risk of the primary endpoint. Conclusions Patients who attained a significant reduction in NT-proBNP had a lower subsequent rate of cardiovascular death or HF hospitalization independent of the treatment group. Treatment with sacubitril/valsartan was nearly twice as likely as enalapril to reduce NT-proBNP to values ≤1,000 pg/ml. (Prospective Comparison of ARNI Angiotensin Receptor–Neprilysin Inhibitor with ACEI Angiotensin-Converting–Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial) PARADIGM-HF; NCT01035255 .)
While disease-modifying therapies exist for heart failure (HF) with reduced left ventricular ejection fraction (LVEF), few options are available for patients in the higher range of LVEF (>40%). ...Sacubitril/valsartan has been compared with a renin-angiotensin-aldosterone-system inhibitor alone in 2 similarly designed clinical trials of patients with reduced and preserved LVEF, permitting examination of its effects across the full spectrum of LVEF.
We combined data from PARADIGM-HF (LVEF eligibility≤40%; n=8399) and PARAGON-HF (LVEF eligibility≥45%; n=4796) in a prespecified pooled analysis. We divided randomized patients into LVEF categories: ≤22.5% (n=1269), >22.5% to 32.5% (n=3987), >32.5% to 42.5% (n=3143), > 42.5% to 52.5% (n=1427), > 52.5% to 62.5% (n=2166), and >62.5% (n=1202). We assessed time to first cardiovascular death and HF hospitalization, its components, and total heart failure hospitlizations, all-cause mortality, and noncardiovascular mortality. Incidence rates and treatment effects were examined across categories of LVEF.
Among 13 195 randomized patients, we observed lower rates of cardiovascular death and HF hospitalization, but similar rates of noncardiovascular death, among patients in the highest versus the lowest groups. Overall sacubitril/valsartan was superior to renin-angiotensin-aldosterone-system inhibition for first cardiovascular death or heart failure hospitalization (Hazard Ratio HR 0.84 95% CI, 0.78-0.90), cardiovascular death (HR 0.84 95% CI, 0.76-0.92), heart failure hospitalization (HR 0.84 95% CI, 0.77-0.91), and all-cause mortality (HR 0.88 95% CI, 0.81-0.96). The effect of sacubitril/valsartan was modified by LVEF (treatment-by-continuous LVEF interaction
=0.02), and benefit appeared to be present for individuals with EF primarily below the normal range, although the treatment benefit for cardiovascular death diminished at a lower ejection fraction. We observed effect modification by LVEF on the efficacy of sacubitril/valsartan in both men and women with respect to composite total HF hospitalizations and cardiovascular death, although women derived benefit to higher ejection fractions.
The therapeutic effects of sacubitril/valsartan, compared with a renin-angiotensin-aldosterone-system inhibitor alone, vary by LVEF with treatment benefits, particularly for heart failure hospitalization, that appear to extend to patients with heart failure and mildly reduced ejection fraction. These therapeutic benefits appeared to extend to a higher LVEF range in women compared with men.
https://www.clinicaltrials.gov. Unique identifiers: NCT01920711 (PARAGON-HF), NCT01035255 (PARADIGM-HF).
PDF
