Syed Kazmi

What proportion of patients with chronic heart failure are eligible for sacubitril–valsartan?

The PARADIGM‐HF trial showed that sacubitril–valsartan, an ARB–neprilysin inhibitor, is more effective than enalapril for some patients with heart failure (HF). It is uncertain what proportion of patients with HF would be eligible for sacubitril–valsartan in clinical practice.

Depression as an independent prognostic factor for all-cause mortality after a hospital admission for worsening heart failure

BACKGROUND Depression is associated with increased mortality amongst patients with chronic heart failure (HF). Whether depression is an independent predictor of outcome in patients admitted for worsening of HF is unclear. METHODS OPERA-HF is an observational study enrolling patients hospitalized with worsening HF. Depression was assessed by the Hospital Anxiety and Depression Scale (HADS-D) questionnaire. Comorbidity was assessed by the Charlson Comorbidity Index (CCI). Kaplan-Meier and Cox regression analyses were used to estimate the association between depression and all-cause mortality. RESULTS Of 242 patients who completed the HADS-D questionnaire, 153, 54 and 35 patients had no (score 0-7), mild (score 8-10) or moderate-to-severe (score 11-21) depression, respectively. During follow-up, 35 patients died, with a median time follow-up of 360days amongst survivors (interquartile range, IQR 217-574days). In univariable analysis, moderate-to-severe depression was associated with an increased risk of death (HR: 4.9; 95% CI: 2.3 to 10.2; P<0.001) compared to no depression. Moderate-to-severe depression also predicted all-cause mortality after controlling for age, CCI score, NYHA class IV, NT-proBNP and treatment with mineralocorticoid receptor antagonist, beta-blocker and diuretics (HR: 3.0; 95% CI: 1.3 to 7.0; P<0.05). CONCLUSIONS Depression is strongly associated with an adverse outcome in the year following discharge after an admission to hospital for worsening HF. The association is only partly explained by the severity of HF or comorbidity. Further research is required to demonstrate whether recognition and treatment of depression improves patient outcomes.

Long-term changes of renal function in relation to ace inhibitor/angiotensin receptor blocker dosing in patients with heart failure and chronic kidney disease.

BACKGROUND Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have become cornerstones of therapy for chronic heart failure (CHF). Guidelines advise high target doses for ACEIs/ARBs, but fear of worsening renal function may limit dose titration in patients with concomitant chronic kidney disease (CKD). METHODS In this retrospective observational study, we identified 722 consecutive patients with systolic CHF, stable CKD stage III/IV (estimated glomerular filtration rate [eGFR] 15-60 mL min(-1) 1.73 m(-2)) and chronic ACEI/ARB treatment from the outpatient heart failure clinics at the Universities of Hull, UK, and Heidelberg, Germany. Change of renal function, worsening CHF, and hyperkalemia at 12-month follow-up were analyzed as a function of both baseline ACEI/ARB dose and dose change from baseline. RESULTS ΔeGFR was not related to baseline dose of ACEI/ARB (P = .58), or to relative (P = .18) or absolute change of ACEI/ARB dose (P = .21) during follow-up. Expressing change of renal function as a categorical variable (improved/stable/decreased) as well as subgroup analyses with respect to age, sex, New York Heart Association functional class, left ventricular ejection fraction, diabetes, concomitant aldosterone antagonists, CKD stage, hypertension, ACEI vs ARB, and congestion status yielded similar results. There was no association of dose/dose change with incidence of either worsening CHF or hyperkalemia. CONCLUSIONS In patients with systolic CHF and stable CKD stage III/IV, neither continuation of high doses of ACEI/ARB nor up-titration was related to adverse changes in longer-term renal function. Conversely, down-titration was not associated with improvement in eGFR. Use of high doses of ACEI/ARB and their up-titration in patients with CHF and CKD III/IV may be appropriate provided that the patient is adequately monitored.

Prognostic value of psychosocial factors for first and recurrent hospitalizations and mortality in heart failure patients: insights from the OPERA-HF study.

Psychosocial factors are rarely collected in studies investigating the prognosis of patients with heart failure (HF), and only time to first event is commonly reported. We investigated the prognostic value of psychosocial factors for predicting first or recurrent events after discharge following hospitalization for HF.

Low serum chloride in patients with chronic heart failure: clinical associations and prognostic significance: Chloride in chronic heart failure

Low serum chloride is common in patients with chronic heart failure (CHF) and is associated with worse outcomes. We investigated the clinical and prognostic associations, including cause of death associations, of low serum chloride in patients referred to a secondary care clinic with suspected heart failure.

Comparative effectiveness of enalapril, lisinopril, and ramipril in the treatment of patients with chronic heart failure: a propensity score-matched cohort study

Aims Angiotensin-converting enzyme inhibitors (ACEIs) are recommended as first-line therapy in patients with heart failure with reduced ejection fraction (HFrEF). The comparative effectiveness of different ACEIs is not known. Methods and results A total of 4723 outpatients with stable HFrEF prescribed enalapril, lisinopril, or ramipril were identified from three registries in Norway, England, and Germany. In three separate matching procedures, patients were individually matched with respect to both dose equivalents and their respective propensity scores for ACEI treatment. During a follow-up of 21 939 patient-years, 360 (49.5%), 337 (52.4%), and 1119 (33.4%) patients died among those prescribed enalapril, lisinopril, and ramipril, respectively. In univariable analysis of the general sample, enalapril and lisinopril were both associated with higher mortality when compared with ramipril treatment [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.30-1.65, P < 0.001 and HR 1.38, 95% CI 1.22-1.56, P < 0.001, respectively). Patients prescribed enalapril or lisinopril had similar mortality (HR 1.06, 95% CI 0.92-1.24, P = 0.41). However, there was no significant association between ACEI choice and all-cause mortality in any of the matched samples (HR 1.07, 95% CI 0.91-1.25, P = 0.40; HR 1.12, 95% CI 0.96-1.32, P = 0.16; and HR 1.10, 95% CI 0.93-1.31, P = 0.25 for enalapril vs. ramipril, lisinopril vs. ramipril, and enalapril vs. lisinopril, respectively). Results were confirmed in subgroup analyses with respect to age, sex, left ventricular ejection fraction, New York Class Association functional class, cause of HFrEF, rhythm, and systolic blood pressure. Conclusion Our results suggest that enalapril, lisinopril, and ramipril are equally effective in the treatment of patients with HFrEF when given at equivalent doses.

45 Role of Natriuretic Peptides in Screening of Cardiac Dysfunction in Older Patients with Type-2 Dibetes Mellitus. A Report from Sica-diabetes Study (FP7/2007–2013/241558)

Purpose Type-2 diabetes mellitus (T2DM) is risk factor for developing cardiac dysfunction and heart failure. The plasma concentration of amino-terminal pro-brain natriuretic peptide (NT-proBNP) could be a simple tool for screening for cardiac dysfunction amongst older patients with T2DM. Method Patients receiving treatment for T2DM for at least 12 months, aged >40 years and not already known to have heart or renal failure were invited to complete a symptom questionnaire and to have NT-proBNP measuredas part of their annual check-up in primary care. Patients also had a physical examination, routine laboratory tests and were tested for neuropathy and retinopathy. All patients with increased NT-proBNP values and a sample of others was invited to attend for further cardiac investigations. Results Of 1224 patients screened, the median age was 65 (IQR: 58–72) years and 520 (42%) were women. NT-proBNP was >500 ng/L in 54 (4%), 250–500 ng/L in 83 (7%), 125–250 ng/L in 212 (17%), 50–125 ng/L in 424 (34%) and <50ng/L in 451 (37%). Patients with higher NT-proBNP had lower body mass index, smaller waist circumference and higher serum creatinine but had similar heart rate and blood pressure. Of the 54 patients with values >500 ng/L, 43% had symptoms suggesting heart failure, and 20% had serum creatinine >150 umol/L (median: 100 (IQR: 81–140) µmol/L). In patients with NT-proBNP >500 ng/L, 2% had serum creatinine >150 umol/L (median: 77(65–91) µmol/L) and 19% had maculopathy or Grade 2 or worse retinopathy. Onechocardiography, all but two patients had major cardiac dysfunction; 24% had left ventricular ejection fraction <50%, 78% a dilated left atrium >38 mm, 30% had elevated systolic pulmonary artery pressures (>40 mmHg) and 42% patients were in atrial fibrillation. During a median follow-up of 436 (IQR: 334–503) days, the percentage of patients with a cardiovascular admission rose progressively from 8%, 13%, 19% to 28% and all-cause mortality from 0.6%, 0.6%, 1.2%, 3.9% to 9.8% for each of the NT-proBNP strata. Conclusions NT-proBNP is a simple method of screening for cardiac dysfunction inT2DM. A high proportion of those with elevated values have a dilated left atrium and pulmonary hypertension possibly reflecting left ventricular diastolic dysfunction.

6 Prognostic value of malnutrition screening tools in patients with chronic heart failure

Background Malnutrition is a common clinical feature in patients with acute heart failure (AHF), but its prevalence and clinical impact on morbidity and mortality of patients with chronic HF (CHF) remains to be determined. Purpose To evaluate the prevalence, clinical associations and prognostic value of three different malnutrition indices in a large cohort of patients referred to a community HF clinic with suspected HF. Methods Consecutive referrals were analysed. HF was defined as signs or symptoms and evidence of cardiac dysfunction, either a reduced left ventricular ejection fraction at echocardiography (LVEF, <50%) or raised NTproBNP (>125 ng/L). Patients were screened for malnutrition using three common malnutrition indices: the geriatric nutritional risk index (GNRI), the controlling nutritional status (CONUT) score and the prognostic nutritional index (PNI). Results Of the 5012 patients who attended between 2000 and 2016, HF was confirmed in 3386 (61% males, median age 75 (interquartile range (IQR): 67–81) years, median NTproBNP 1573 (IQR: 702–2799) ng/L). Of these, 1198 (35%) and 1458 (43%) patients had HF with reduced (HeFREF, LVEF<40%) and normal (HeFNEF, LVEF 50%) ejection fraction, respectively. According to the GNRI (91%), CONUT score (>4) and PNI (38%), 6.7%, 10.0% and 7.5% patients were moderately to severely malnourished, respectively. Compared to those with normal nutritional status, malnourished patients were older, had lower body mass index (BMI), worse symptoms and renal function; they were also more likely to have atrial fibrillation, anaemia and reduced mobility. During a median follow-up of 1573 days (interquartile range: 702–2799 days), 1723 (50.9%) patients died. In multivariable models, indices of malnutrition were powerful predictors of mortality. In a multivariable model that included all the malnutrition indices, only GNRI was independently associated with increased risk of mortality (Hazard ratio (95% confidence interval): 1.25 (1.12–1.39), p<0.001 for worsening malnutrition category of GNRI). Conclusion Moderate or severe malnutrition is highly prevalent amongst patients with CHF and is strongly related to mortality.

Optimization of Non Adaptive Mechanical Ventilation by Analyzing Electrical Impedance Tomography Images Using Advance Statistical Methods as Analytic Tool

Non adaptive mechanical ventilation could be optimized by analyzing ventilation inhomogeneity in lungs using different methods. Mechanical ventilator could be equipped with adaptive characteristics by delivering feedback according to patient lung conditions. In this study, various statistical analysis techniques are employed on lung images acquired by Electrical Impedance Tomography (EIT) in order to characterize degree of inhomogeneity in severely ill patients, being treated on ventilators. The statistical methods employed include Jackknife, bootstrap and self consistency test. Since acquired lung images have random variation, Jackknifing is critical in drawing robust conclusions about inhomogeneous distribution of ventilation. As relative impedance values in EIT images are directly acquired from patient (free distribution), Bootstrap method delivered vigorous results about sampling distribution of relative impedance data. Self consistency test results compute degree of inhomogeneity not only between healthy and diseased lungs but also among diseased lung regions of single patient. Standalone application software tool is developed with above methods as background algorithm to facilitate researchers and engineers to optimize non-adaptive mechanical ventilation.