Eligibility for sacubitril/valsartan in heart failure across the ejection fraction spectrum: real-world data from the Swedish Heart Failure Registry.

BACKGROUND: Randomized controlled trials (RCT) generalizability may be limited due to strict patient selection. OBJECTIVE: In a real-world heart failure (HF) population, we assessed eligibility for sacubitril/valsartan based on PARADIGM-HF (sacubitril/valsartan effective)/PARAGON-HF [sacubitril/valsartan effective in mildly reduced ejection fraction (EF)]. METHODS: Outpatients from the Swedish HF Registry (SwedeHF) were analysed. In SwedeHF, EF is recorded as <30, 30-39, 40-49 and ≥50%. In PARAGON-HF, sacubitril/valsartan was effective with EF ≤ 57% (i.e. median). We defined reduced EF/PARADIGM-HF as EF < 40%, mildly reduced EF/PARAGON-HF ≤ median as EF 40-49%, and normal EF/PARAGON-HF > median as EF ≥ 50%. We assessed 2 scenarios: (i) criteria likely to influence treatment decisions (pragmatic scenario); (ii) all criteria (literal scenario). RESULTS: Of 37 790 outpatients, 57% had EF < 40%, 24% EF 40-49% and 19% EF ≥ 50%. In the pragmatic scenario, 63% were eligible in EF < 50% (67% for EF < 40% and 52% for 40-49%) and 52% in EF ≥ 40% (52% for EF ≥ 50%). For the literal scenario, 32% were eligible in EF < 50% (38% of EF < 40%, 20% of EF 40-49%) and 22% in EF ≥ 40% (25% for EF ≥ 50%). Eligible vs. noneligible patients had more severe HF, more comorbidities and overall worse outcomes. CONCLUSION: In a real-world HF outpatient cohort, 81% of patients had EF < 50%, with 63% eligible for sacubitril/valsartan based on pragmatic criteria and 32% eligible based on literal trial criteria. Similar eligibility was observed for EF 40-49% and ≥50%, suggesting that our estimates for EF < 50% may be reproduced whether or not a higher cut-off for EF is considered.

"Real World" Eligibility for Sacubitril/Valsartan in Unselected Heart Failure Patients: Data from the Swedish Heart Failure Registry.

PURPOSE: PARADIGM-HF demonstrated the superiority of sacubitril/valsartan over enalapril in patients with heart failure and reduced ejection fraction (HF-REF). How widely applicable sacubitril/valsartan treatment is in unselected patients with HF-REF is not known. We examined eligibility of patients with HF-REF for treatment with sacubitril/valsartan, according to the criteria used in PARADIGM-HF, in the Swedish Heart Failure Registry (SwedeHF). METHODS: Patients were considered potentially eligible if they were not hospitalized, had symptoms (NYHA class II-IV) and a reduced LVEF (≤ 40%), and were prescribed an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) at a dose equivalent to enalapril ≥ 10 mg daily. In these patients, we evaluated further eligibility according to the main additional PARADIGM-HF inclusion criteria. RESULTS: Of 12,866 outpatients in NYHA functional class II-IV with an LVEF ≤ 40%, 9577 were prescribed at least 10 mg of enalapril (or equivalent) daily. Complete additional data were available for 3099 of these patients (32.4%) and of them 75.5% were potentially eligible for treatment with sacubitril/valsartan. The most common reason for ineligibility was a low natriuretic peptide level (n = 462, 14.9%). Only a small proportion of patients were ineligible due to low eGFR or serum potassium level. Because only 78% of patients were taking ≥ 10 mg enalapril or equivalent daily, only 58.9% of all patients (75.5% of 78%) were eligible for sacubitril/valsartan. CONCLUSIONS: Between 34 and 76% of symptomatic patients with HF-REF in a 'real world' population are eligible for treatment with sacubitril/valsartan, depending on background ACEI/ARB dose. The most common reason for ineligibility is a low natriuretic peptide level.

Comorbidities, risk factors and outcomes in patients with heart failure and an ejection fraction of more than or equal to 40% in primary care- and hospital care-based outpatient clinics.

OBJECTIVE: The aim of this study is to describe patients with heart failure and an ejection fraction (EF) of more than or equal to 40%, managed in both Primary- and Hospital based outpatient clinics separately with their prognosis, comorbidities and risk factors. Further to compare the heart failure medication in the two groups. DESIGN: We used the prospective Swedish Heart Failure Registry to include 9654 out-patients who had HF and EF ≥40%, 1802 patients were registered in primary care and 7852 in hospital care. Descriptive statistical tests were used to analyze base line characteristics in the two groups and multivariate logistic regression analysis to assess mortality rate in the groups separately. SETTING: The prospective Swedish Heart Failure Registry. SUBJECTS: Patients with heart failure and an ejection fraction (EF) of more than or equal to 40%. MAIN OUTCOME MEASURES: Comorbidities, risk factors and mortality. RESULTS: Mean-age was 77.5 (primary care) and 70.3 years (hospital care) p < 0.0001, 46.7 vs. 36.3% women respectively (p < 0.0001) and EF ≥50% 26.1 vs. 13.4% (p < 0.0001). Co-morbidities were common in both groups (97.2% vs. 92.3%), the primary care group having more atrial fibrillation, hypertension, ischemic heart disease and COPD. According to the multivariate logistic regression analysis smoking, COPD and diabetes were the most important independent risk factors in the primary care group and valvular disease in the hospital care group. All-cause mortality during mean follow-up of almost 4 years was 31.5% in primary care and 27.8% in hospital care. One year-mortality rates were 7.8%, and 7.0% respectively. CONCLUSION: Any co-morbidity was noted in 97% of the HF-patients with an EF of more than or equal to 40% managed at primary care based out-patient clinics and these patients had partly other independent risk factors than those patients managed in hospital care based outpatients clinics. Our results indicate that more attention should be payed to manage COPD in the primary care group. KEY POINTS 97% of heart failure patients with an ejection fraction of more than or equal to 40% managed at primary care based out-patient clinics had any comorbidity. Patients in primary care had partly other independent risk factors than those in hospital care. All-cause mortality during mean follow-up of almost 4 years was higher in primary care compared to hospital care. In matched HF-patients RAS-antagonists, beta-blockers as well as the combination of the two drugs were more seldom prescribed when managed in primary care compared with hospital care.

Effect of nesiritide in patients with acute decompensated heart failure.

BACKGROUND: Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. METHODS: We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. RESULTS: Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.1 to 0.7; P=0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, -0.4 percentage points; 95% CI, -1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P=0.11). CONCLUSIONS: Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.).

Sex-related differences among young adults with heart failure in Sweden.

BACKGROUND: Differences between the sexes among the non-elderly with heart failure (HF) have been insufficiently evaluated. This study aims to investigate sex-related differences in early-onset HF. METHODS: Patients aged 18 to 54 years who were registered from 2003 to 2014 in the Swedish Heart Failure Register were included. Each patient was matched with two controls from the Swedish Total Population Register. Data on comorbidities and outcomes were obtained through the National Patient Register and Cause of Death Register. RESULTS: We identified 3752 patients and 7425 controls. Of the patients, 971 (25.9%) were women and 2781 (74.1%) were men with a mean (standard deviation) age of 44.9 (8.4) and 46.4 (7.3) years, respectively. Men had more hypertension and ischemic heart disease, whereas women had more congenital heart disease and obesity. During the median follow-up of 4.87 years, 26.5 and 24.7 per 1000 person-years male and female patients died, compared with 3.61 and 2.01 per 1000 person-years male and female controls, respectively. The adjusted hazard ratios for all-cause mortality, compared with controls, were 4.77 (3.78-6.01) in men and 7.84 (4.85-12.7) in women (p for sex difference = 0.11). When HF was diagnosed at 30, 35, 40, and 45 years, women and men lost up to 24.6 and 24.2, 24.4 and 20.9, 20.5 and 18.3, and 20.7 and 16.5 years of life, respectively. CONCLUSION: Long-term mortality was similar between the sexes. Women lost more years of life than men.

Impaired abdominal aortic wall integrity in elderly men carrying the angiotensin-converting enzyme D allele.

OBJECTIVE: A polymorphism in the angiotensin-converting-enzyme gene (ACE I/D) has been associated with abdominal aortic aneurysm and a link between aortic aneurysm and aortic stiffness has been suggested. This study aimed to explore the links between ACE I/D polymorphism, circulating ACE and abdominal aortic wall integrity as reflected by abdominal aortic wall stiffness. MATERIAL: A total of 212 men and 194 women, aged 70-88 years, were studied. METHODS: Mechanical properties of the abdominal aorta were determined using the Wall Track System, ACE genotype using the polymerase chain reaction (PCR) and circulating ACE level by enzyme-linked immunosorbent assay (ELISA). RESULTS: In men, pulsatile diameter change differed between genotypes (II 0.70, ID 0.55 and DD 0.60 mm, P = 0.048), whereas a tendency was seen for distensibility coefficient (DC) (II 10.38, ID 7.68 and ID 8.79, P = 0.058). Using a dominant model (II vs. ID/DD), men carrying the ACE D allele had lower pulsatile diameter change (P = 0.014) and DC (P = 0.017) than II carriers. Multiple regression analyses showed additional associations between the D allele and increased stiffness ß, and reduced compliance coefficient. CONCLUSION: Men carrying the ACE D allele have stiffer abdominal aortas compared with II carriers. Deranged abdominal aortic stiffness indicates impaired vessel wall integrity, which, along with other local predisposing factors, may be important in aneurysmal disease.

Association of genetic variation on chromosome 9p21.3 and arterial stiffness.

OBJECTIVES: Genome wide association studies have consistently reported associations between a region on chromosome 9p21.3 and a broad range of vascular diseases, such as coronary artery disease (CAD), aortic and intracranial aneurysms and type-2 diabetes (T2D). However, clear associations with intermediate phenotypes have not been described so far. To shed light on a possible influence of this chromosomal region on arterial wall integrity, we analysed associations between single nucleotide polymorphisms (SNPs) and degree of stiffness of the abdominal aorta in elderly individuals. METHODS AND RESULTS: A total of 400 subjects, 212 men and 188 women, aged 70-88 years were included. Arterial stiffness was examined at the midpoint between the renal arteries and the aortic bifurcation. Two CAD- and aneurysm-associated SNPs (rs10757274 and rs2891168) and one T2D-associated SNP (rs1081161) within the 9p21.3 region were genotyped. Aortic compliance and distensibility coefficients were higher in carriers of the rs10757274G and rs2891168G alleles in men reflecting a decrease in aortic stiffness. Adjustment for age and mean arterial pressure had no effect on these associations. The two SNPs were not associated with intima-media thickness or lumen diameter of the abdominal aorta. There were no associations between the rs10811661 SNP and any measure of aortic stiffness. CONCLUSIONS: Impaired mechanical properties of the arterial wall may explain the association between chromosome 9p21.3 polymorphisms and vascular disease.

Patients with heart failure in primary health care: effects of a nurse-led intervention on health-related quality of life and depression.

AIMS: To determine the effects of a nurse-led intervention designed to improve self-management of patients with heart failure in a primary health care setting regarding health-related quality of life and depression. METHODS: Patients at eight primary health care centres were screened by the Diagnosis Related Groups registry for the diagnosis of heart failure and eligibility for a cluster randomised study. A total of 153 patients were included (n=78 in the intervention group, 54% males, mean age 79 years, 59% in New York Heart Association class III-IV). The intervention involved patient and family education about heart failure and self-management and monthly telephone follow-up during 12 months by a primary health care nurse. RESULTS: The effects of the nurse-led intervention were limited. Significant differences were found in the physical dimension measured by the SF-36 health survey, and in depression measured by the Zung Self-rating Depression Scale. In comparison within groups at the 3 and 12-month follow-up, the intervention group significantly maintained their health-related quality of life measured by the SF-36 health survey, and their experience of depression measured by the Zung Self-rating Depression Scale to a greater extent than in the control group, especially among women. CONCLUSION: A nurse-led intervention directed toward patients with heart failure in a primary health care setting resulted in limited effects between the groups, although the physical and mental status were retained during 12 months of follow-up to a greater extent than in the control group.

The risk of cardiovascular death in elderly patients with possible heart failure. Results from a 6-year follow-up of a Swedish primary care population.

UNLABELLED: Little is known about the prognosis and clinical variables influencing the prognosis among elderly patients in primary health care with mild to moderate heart failure. AIM: To evaluate the risk of cardiovascular mortality in elderly patients with symptoms of heart failure with respect to systolic and diastolic function, and functional impairment. To evaluate prognostic determinants and to risk-stratify the patients. METHODS: A cardiologist examined 510 patients, out of 548 invited, attending primary care for symptoms of dyspnoea, fatigue and/or peripheral oedema and assessed New York Heart Association (NYHA) functional class. Examination by Doppler echocardiography was done in 454 patients, 56 patients being excluded because of, e.g., atrial fibrillation. Abnormal systolic function was defined as ejection fraction<40%. The diastolic function was evaluated using the mitral inflow and pulmonary venous flow variables. Different clinical and echocardiographic variables were analysed using a Cox regression analysis to identify those most influencing the risk of cardiovascular mortality. CONCLUSION: Abnormal systolic and/or diastolic function was found in 219 patients (48% of the 454 patients who could be echocardiographically completely investigated). The follow-up period was 6 years. Total mortality was 20%, and cardiovascular mortality was 14% (70% of total mortality). Cardiovascular mortality was high in patients with severely impaired functional capacity and ejection fraction<40% at the start of the study. Risk variables identified were male gender, diabetes mellitus, impaired functional capacity and abnormal cardiac function by echocardiography. A prognostic score model using simple clinical variables (gender, NYHA class, cardiac function) was developed to assess the risk of cardiovascular death in order to identify patients with high, moderate or low risk. In a ROC curve analysis, the AUC for clinical variables was only 0.75, whereas the AUC for clinical variables and echocardiography was 0.78, indicating that the additional prognostic information obtained by Doppler echocardiography was rather small.

Risk of cardiovascular death in elderly patients with possible heart failure. B-type natriuretic peptide (BNP) and the aminoterminal fragment of ProBNP (N-terminal proBNP) as prognostic indicators in a 6-year follow-up of a primary care population.

UNLABELLED: Heart failure is common in the elderly population and carries a serious prognosis. We evaluated EDTA-plasma B-type natriuretic peptide (brain natriuretic peptide, BNP) and the aminoterminal fragment of proBNP (N-terminal proBNP) as prognostic markers in elderly primary care patients with symptoms of heart failure. METHODS: From 474 patients attending primary care for symptoms of dyspnea, fatigue and/or peripheral edema, blood was sampled in plastic tubes containing EDTA to measure BNP by non-extraction immunoradiometric assay and N-terminal proBNP by non-extraction radioimmunoassay. Patients were evaluated with respect to history and function by NYHA classification and Doppler echocardiography. Follow-up time was 6 years. Cox regression analysis was performed to identify the weight of risk variables. CONCLUSION: Total 6-year mortality was 20% (102 patients out of 510), and cardiovascular (CV) mortality was 14% (71 patients, 70% of total mortality). BNP and N-terminal proBNP were essentially equally useful as prognostic markers. In patients with the highest quartiles of plasma concentration of BNP and N-terminal proBNP, respectively, the risk of cardiovascular mortality was 10 and 4.8 times, respectively, higher than that in those in the lowest quartile. Peptide concentrations varied widely within all functional groups including those with normal echocardiographic findings. Plasma concentrations of BNP and N-terminal proBNP give important prognostic information concerning risk of cardiovascular mortality. Cost-effective "clinical pathways" should be outlined for patients with elevated peptide concentrations.

Detection of the third heart sound using a tailored wavelet approach: method verification.

Heart sounds can be considered as mechanical fingerprints of myocardial function. The third heart sound normally occurs in children but disappears with maturation. The sound can also appear in patients with heart failure. The sound is characterised by its low-amplitude and low-frequency content, which makes it difficult to identify by the traditional use of the stethoscope. A wavelet-based method has recently been developed for detection of the third heart sound. This study investigated if the third heart sound could be identified in patients with heart failure using this detection method. The method was also compared with auscultation using conventional phonocardiography and with characterisation of the patients with echocardiography. In the first study, 87% of the third heart sounds were detected using the wavelet method, 12% were missed, and 6% were false positive. In study 2, the wavelet-detection method identified 87% of the patients using the third heart sound, and regular phonocardiography identified two (25%) of the subjects.

Improved Health-Related Quality of Life, and More Days out of Hospital with Supplementation with Selenium and Coenzyme Q10 Combined. Results from a Double Blind, Placebo-Controlled Prospective Study.

BACKGROUND: The impact of supplementation with selenium and coenzyme Q10 (CoQ10) on health-care usage and health-related quality of life (Hr-QoL) in community-dwelling elderly people has, to our knowledge, not previously been investigated. AIM: To investigate the effect of 48 months supplementation with CoQ10 and selenium on community-dwelling elderly as regards: (I) the number of days out of hospital, and (II) the effect on Hr-QoL. METHODS: A 48-month double-blind randomized placebo-controlled trial was carried out. A total of 443 participants were given CoQ10 and organic selenium yeast combined, or a placebo. All admissions to the Department of Internal Medicine or Cardiology were evaluated. Hr-QoL were measured with the Short Form-36 (SF-36), the Cardiac Health Profile (CHP) and one item overall-quality of life (overall-QoL). RESULTS: A total of 206 participants were evaluated after 48 months. No changes were found in the number of days out of hospital or Hr-QoL. A sub-analysis of participants matched for age, gender and baseline cardiac wall tension as measured by NT-proBNP was performed. The mean number of days out of hospital was 1779 for those taking the active substance compared to 1533 for those taking the placebo (p=0.03). Those with active substance declined significantly less in the HR-QoL domains of physical role performance (p=0.001), vitality (p=0.001), physical component score (p=0.001), overall QoL (p=0.001), somatic dimension (p=0.001), conative dimension (p=0.001) and global function (p=0.001). CONCLUSION: In a match-group analysis selenium and CoQ10 increased the number of days out of hospital and slowed the deterioration in Hr-QoL.

Hemodynamics and leg muscle metabolism at rest and during exercise in young healthy men after prenalterol.

In eight young healthy men the effects of short-term treatment with prenalterol, a new beta-adrenergic agonist, on peripheral hemodynamics and leg muscle metabolism were studied at rest and during exercise at a moderate and a heavy workload. At rest prenalterol treatment significantly increased pulmonary oxygen uptake, heart rate, rate pressure product, and leg blood flow and decreased leg arteriovenous oxygen content difference. During exercise fewer hemodynamic effects of prenalterol were observed. At the moderate workload there was a slight increase in heart rate, but at the heavy workload heart rate fell. Prenalterol raised the arterial concentrations of free fatty acids and glycerol at rest by 70% and 40%, but during exercise these alterations were not present. The plasma levels of epinephrine and dopamine in subjects at rest decreased significantly during influence of prenalterol, but these differences were also abolished during exercise. The leg exchange of metabolites and the concentrations of endogenous muscle metabolites were not influenced by prenalterol, although the lactate concentrations in muscle tended to be lower at rest and during exercise. The results at rest demonstrate that prenalterol in this situation acts predominantly as a stimulator of beta 1-adrenoceptors. During heavy exercise, however, when the endogenous sympathetic tone is high, the beta-stimulating effects are no longer overt and instead reduced heart rate indicates a blocking effect on beta-adrenoceptors. The hemodynamic and metabolic results are concordant with the hypothesis that prenalterol acts as a partial beta-receptor agonist.

Captopril and spironolactone therapy for refractory congestive heart failure.

Short- and long-term clinical effects of the angiotensin-converting enzyme (ACE) inhibitor captopril in severe congestive heart failure (CHF) were evaluated during a 3-year open study of 124 inpatients with New York Heart Association (NYHA) functional class III or IV CHF refractory to treatment with cardiac glycosides and high doses of loop diuretics. Captopril was added to each patient's regimen, which comprised combinations of furosemide (124 patients), digitalis (117 patients), and spironolactone (90 patients). By the end of the first month of captopril administration, improvement in NYHA functional class was seen in 89 patients (72%). During the first year of captopril treatment, the number of hospital admissions and hospital days declined significantly (p < 0.001) and functional class improved significantly (p < 0.001). Although most patients tolerated captopril well, 44% experienced hypotension, which in 10% of patients necessitated termination of captopril therapy. Although mean serum potassium levels tended to increase, serious hyperkalemia did not occur. After 1 year, a subset of 30 patients who had not initially received spironolactone deteriorated clinically and manifested increasing urinary aldosterone levels. Hypotension precluded increasing the captopril dose, but introduction of spironolactone improved clinical status in this cohort. The results suggest that rational therapy for severe CHF includes addition of the aldosterone antagonist spironolactone to low doses of captopril (or another ACE inhibitor) and high doses of loop diuretics, provided renal function is adequate.

Can natriuretic peptides be used for the diagnosis of diastolic heart failure?

Many patients with heart failure have stiff hearts with an increased wall thickness and small volumes leading to diastolic dysfunction. Different definitions for diastolic heart failure have been proposed but today there is no generally accepted definition and there are few large controlled studies telling us how it should be managed. Natriuretic peptides (BNP or NT-proBNP) might be used to detect patients with diastolic dysfunction especially in those patients having a restrictive filling pattern or pseudo-normalised mitral flow pattern and in those, who are symptomatic. However, patients with relaxation abnormalities and mild symptoms or asymptomatic may have normal levels of the natriuretic peptides indicating no or only slight elevation of the left ventricular filling pressures. Thus low levels cannot be used as a rule out diagnosis of diastolic dysfunction.

Nurse-led heart failure clinics in Sweden.

OBJECTIVE: The aim of this study was to describe the nurse-led heart failure care in Sweden. METHODS: A postal questionnaire was sent to all 86 hospitals in Sweden treating heart failure patients. All hospitals completed the questionnaire, which contained 20 questions about heart failure nurses, patient education, heart failure clinics, co-operation with primary healthcare and care programmes. RESULTS: Sixty-nine percent of all hospitals (n=86) had nurses specialised in taking care of heart failure patients, in total 148 heart failure nurses. The nurses were involved in patient education and follow-up. There were nurse-led heart failure clinics in 66% of the hospitals. The clinics provided follow-up after hospitalisation, telephone counselling and drug titration. The majority of the heart failure nurses had been delegated the responsibility for making protocol-led changes in medications. Most clinics registered the number of annual visits to the clinic, and the largest clinic had up to 1000 visits. Approximately half of the hospitals had a special care plan for patients with heart failure and an organised co-operation with primary healthcare. CONCLUSION: The first nurse-led heart failure clinic started in Sweden in 1990 and since then the model has been spread to two-thirds of the Swedish hospitals.

Effect of carvedilol on diastolic function in patients with diastolic heart failure and preserved systolic function. Results of the Swedish Doppler-echocardiographic study (SWEDIC).

AIM: The purpose of this study was to investigate the effects of carvedilol on diastolic function (DF) in heart failure patients with preserved left ventricular (LV) systolic function and abnormal DF. PATIENTS AND METHODS: We randomised 113 patients with diastolic heart failure (DHF) (symptomatic, with normal systolic LV function and abnormal DF) into a double blind multi-centre study. The patients received either carvedilol or matching placebo in addition to conventional treatment. After uptitration, treatment was continued for 6 months. Two-dimensional and Doppler echocardiography were used for quantification of LV function at baseline and at follow-up. Four different DF variables were evaluated by Doppler echocardiography: mitral flow E:A ratio, deceleration time (DT), isovolumic relaxation time (IVRT) and the ratio of systolic/diastolic pulmonary venous flow velocity (pv-S/D). Primary endpoint was change in the integrated quantitative assessment of all four variables during the study. RESULTS: Ninety-seven patients completed the study. A mitral flow pattern reflecting a relaxation abnormality was recorded in 95 patients. There was no effect on the primary endpoint, although a trend towards a better effect in carvedilol treated patients was noticed in patients with heart rates above 71 beats per minute. At the end of the study, there was a statistically significant improvement in E:A ratio in patients treated with carvedilol (0.72 to 0.83) vs. placebo (0.71 to 0.76), P<0.05. CONCLUSIONS: Treatment with carvedilol resulted in a significant improvement in E:A ratio in patients with heart failure due to a LV relaxation abnormality. E:A ratio was found to be the most useful variable to identify diastolic dysfunction in this patient population. This effect was observed particularly in patients with higher heart rates at baseline.

The Linköping-Lund surgical experience with the HeartMate left ventricular assist system.

Four transplant candidates fulfilling the Food and Drug Administration criteria for a permanent left ventricular assist device received a pneumatic HeartMate system as a bridge to heart transplantation. All patients survived and were fully rehabilitated at the time of transplantation, which was carried out 2 to 6 months after the initial operation. There were no major complications associated with the procedures. We are impressed by the effectiveness and safety of the device.

Treatment with ramipril improves systolic function even in patients with mild systolic dysfunction and symptoms of heart failure after acute myocardial infarction.

BACKGROUND: Clinical signs of heart failure such as pulmonary rales and dyspnea, ventricular dysfunction, and ventricular arrhythmia are independent predictors of a poor prognosis after acute myocardial infarction (AMI). HYPOTHESIS: The study aimed to assess the effect of ramipril treatment on mildly depressed left ventricular (LV) systolic function, assessed by atrioventricular (AV) plane displacement in patients with congestive heart failure after AMI. METHODS: The study was a substudy in the Acute Infarction Ramipril Efficacy Study, a double-blind, randomized, place-bo-controlled trial of ramipril versus placebo in patients with symptoms of heart failure after AMI. In all, 56 patients were included in the main study, 4 refused to participate in the substudy, and 4 were excluded for logistical reasons. Echocardiography was performed at entry and after 6 months. Patients who underwent coronary artery bypass grafting during the follow-up period were excluded. RESULTS: At baseline, the patients had modest LV dysfunction, and mean AV plane displacement of 9.7 mm. During follow-up, AV plane displacement increased in ramipril-treated patients from 9.5 to 10.9 mm (p < 0.01). No statistically significant changes were seen in the placebo group. CONCLUSIONS: Ramipril improves LV systolic function in patients with clinical signs of heart failure and only modest systolic dysfunction after AMI. Measurement of AV plane displacement is a simple and reproducible method for detection of small changes in systolic function and may be used instead of ejection fraction in patients with poor image quality.

The effects of metoprolol and captopril on heart rate variability in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: The effects of treatment with captopril or metoprolol on heart rate variability (HRV) were investigated in 38 patients (29 men and 9 women) with mild to moderate symptoms of heart failure due to idiopathic dilated cardiomyopathy (DCM). HYPOTHESIS: The aim of the study was to investigate and compare the effects of the angiotensin-converting enzyme inhibitor captopril with those of the selective beta-adrenergic receptor blocker metoprolol on HRV in patients with idiopathic DCM. METHODS: Heart rate variability was analyzed in the time and frequency domains from 18th of Holter monitoring before randomized treatment was started, after 6 months of therapy, and 1 month after therapy was stopped. RESULTS: Captopril treatment increased HRV expressed as total power and low-frequency power in the frequency domain. There was no change in the time domain. In the metoprolol group, there was a pronounced increase in both time- and frequency-domain indices of HRV. The increase in total power was partly maintained 1 month after therapy was stopped in both treatment groups. CONCLUSION: Treatment with captopril and metoprolol increases HRV in patients with DCM. This effect seems to be maintained for at least 1 month after therapy is stopped. The increase in HRV seems to be more pronounced with metoprolol, and the two different pharmacologic approaches may have additive effects that are of prognostic importance in patients with heart failure.