Clinical profile of rural community hospital inpatients in Sweden - a register study.

OBJECTIVE: Patients in Sweden's rural community hospitals have not been clinically characterised. We compared characteristics of patients in general practitioner-led community hospitals in northern Sweden with those admitted to general hospitals. DESIGN: Retrospective register study. SETTING: Community and general hospitals in Västerbotten and Norrbotten counties, Sweden. PATIENTS: Patients enrolled at community hospitals and hospitalised in community and general hospitals between 1 January 2010 and 31 December 2014. OUTCOME MEASURES: Age, sex, number of admissions, main, secondary and total number of diagnoses. RESULTS: We recorded 16,133 admissions to community hospitals and 60,704 admissions to general hospitals. Mean age was 76.8 and 61.2 years for community and general hospital patients (p < .001). Women were more likely than men to be admitted to a community hospital after age adjustment (odds ratio (OR): 1.11; 95% confidence interval (CI): 1.09-1.17). The most common diagnoses in community hospital were heart failure (6%) and pneumonia (5%). Patients with these diagnoses were more likely to be admitted to a community than a general hospital (OR: 2.36; 95% CI: 2.15-2.59; vs. OR: 3.32: 95% CI: 2.77-3.98, respectively, adjusted for age and sex). In both community and general hospitals, doctors assigned more diagnoses to men than to women (both p<.001). CONCLUSIONS: Patients at community hospitals were predominantly older and women, while men were assigned more diagnoses. The most common diagnoses were heart failure and pneumonia. Our observed differences should be further explored to define the optimal care for patients in community and general hospitals.Key pointsThe patient characteristics at Swedish general practitioner-led rural community hospitals have not yet been reported. This study characterises inpatients in community hospitals compared to those referred to general hospitals.• Patients at community hospitals were predominantly older, with various medical conditions that would have led to a referral to general hospitals elsewhere in Sweden. • Compared to men, women were more likely to be admitted to community hospitals than to general hospitals, even after adjustment for age. To the best of our knowledge, this pattern has not been reported in other countries with community hospitals. • In both community hospitals and general hospitals, doctors assigned more diagnoses to men than to women.

Leptin levels are not affected by enalapril treatment after an uncomplicated myocardial infarction, but associate strongly with changes in fibrinolytic variables in men.

Leptin, an adipocyte-derived hormone, is involved in the regulation of body weight and is associated with obesity-related complications, notably cardiovascular disease (CVD). A putative link between obesity and CVD could be induction of plasminogen activator inhibitor-1 (PAI-1) synthesis by leptin. In this study, we hypothesized that the beneficial effect of the angiotensin-converting enzyme inhibitor (ACEi) enalapril on PAI-1 levels is mediated by effects on leptin levels. The association between leptin and components of the fibrinolytic system was evaluated in a non-prespecified post hoc analysis of a placebo-controlled randomized, double-blind trial where the effect of the ACEi enalapril on fibrinolysis was tested. A total of 46 men and 37 women were randomized to treatment with enalapril or placebo after (median 12 months) an uncomplicated myocardial infarction. At baseline, the participants were stable and had no signs of congestive heart failure. Leptin and fibrinolytic variables (mass concentrations of PAI-1, tissue plasminogen activator (tPA) and tPA-PAI complex) were measured at baseline, and after 10 days, 6 months and 12 months. Enalapril treatment did not change leptin levels, which increased significantly during 1 year of follow-up (p = .007). Changes in leptin levels were strongly associated with changes of tPA mass (p = .001), tPA-PAI complex (p = .003) and of PAI-1 (p = .006) in men, but not in women. Leptin levels are not influenced by treatment with an ACEi. In contrast, leptin associates strongly with changes in fibrinolytic variables notably with a sex difference, which could be of importance for obesity-related CVD.

Flawed conclusions on the Västerbotten Intervention Program by San Sebastian et .al.

An evaluation of Västerbotten Intervention Programme (VIP) was recently conducted by San Sebastian et al. (BMC Public Health 19:202, 2019). Evaluation of health care interventions of this kind require 1) an understanding of both the design and the nature of the intervention, 2) correct definition of the target population, and 3) careful choice of the appropriate evaluation method. In this correspondence, we review the approach used by San Sebastian et al. as relates to these three criteria. Within this framework, we suggest important explanations for why the conclusions drawn by these authors contradict a large body of research on the effectiveness of the VIP.

NTproBNP and ST2 as predictors for all-cause and cardiovascular mortality in elderly patients with symptoms suggestive for heart failure.

BACKGROUND: A new biomarker, suppression of tumorigenicity 2 (ST2) has been introduced as a marker for fibrosis and hypertrophy. Its clinical value in comparison with N-terminal pro-hormone of brain natriuretic peptide /Amino-terminal pro-B-type natriuretic peptide (NTproBNP) in predicting mortality in elderly patients with symptoms of heart failure (HF) is still unclear. AIM: To evaluate the prognostic value for all-cause- and cardiovascular mortality of ST2 or NTproBNP and the combination of these biomarkers. PATIENTS AND METHODS: One hundred seventy patients patients with clinical symptoms of HF (77 (45%) were with verified HF) were recruited from one selected primary health care center (PHC) in Sweden and echocardiography was performed in all patients. Blood samples were obtained from 159 patients and stored frozen at -70 °C. NTproBNP was analyzed at a central core laboratory using a clinically available immunoassay.ST2 was analyzed with Critical Diagnostics Presage ST2 ELISA immunoassay. RESULTS: We studied 159 patients (mean age 77 ± 8.3 years, 70% women). During ten years of follow up 78 patients had died, out of which 50 deaths were for cardiovascular reasons. Continuous NTproBNP and ST2 were both significantly associated with all-cause mortality (1.0001; 1.00001-1.0002, p = 0.04 and 1.03; 1.003-1.06, p = 0.03), NTproBNP but not ST2 remained significant for cardiovascular mortality after adjustments (1.0001; 1.00001-1.0002, p = 0.03 and 1.01; 0.77-1.06, p = 0.53), respectively. NTproBNP above median (>328 ng/L) compared to below median was significantly associated with all-cause mortality(HR: 4.0; CI :2.46-6.61; p < 0.001) and cardiovascular mortality (HR: 6.1; CI: 3.11-11.95; p < 0.001). Corresponding analysis for ST2 above median (25.6 ng/L) was not significantly associated neither with all-cause mortality (HR; 1.4; CI: 0.89-2.77) nor cardiovascular mortality (HR: 1.3; CI: 0.73-2.23) and no significant interaction of NTproBNP and ST2 (OR: 1.1; CI: 0.42-3.12) was found. CONCLUSION: In elderly patients with symptoms of heart failure ST2 was not superior to NTproBNP to predict all cause or cardiovascular mortality. Furthermore, it is unclear if the combination of ST2 and NTproBNP will improve long-term prognostication beyond what is achieved by NTproBNP alone.

Areas for quality improvements in heart failure care: quality of care from the family members' perspective.

BACKGROUND: The complex needs of people with chronic heart failure (HF) place great demands on their family members, and it is important to ask family members about their perspectives on the quality of HF care. OBJECTIVE: To describe family members' perceptions of quality of HF care in an outpatient setting. METHODS: A cross-sectional study using a short form of the Quality from Patients' Perspective (QPP) questionnaire for data collection. The items in the questionnaire measure four dimensions of quality, and each item consists of both the perceived reality of the care and its subjective importance. The study included 57 family members of patients with severe HF in NYHA class III-IV. RESULTS: Family members reported areas for quality improvements in three out of four dimensions and in dimensionless items. The lowest level of perceived reality was reported for treatment for confusion and loss of appetite. Treatment for shortness of breath, access to the apparatus and access to equipment necessary for medical care were the items with the highest subjective importance for the family members. CONCLUSION: Family members identified important areas for quality improvement in the care for patients with HF in an outpatient setting. In particular, symptom alleviation, information to patients, patient participation and access to care were identified as areas for improvements. Thus, measuring quality from the family members' perspective with the QPP might be a useful additional perspective when it comes to the planning and implementation of changes in the organisation of HF care.

Family members' experiences of integrated palliative advanced home and heart failure care: A qualitative study of the PREFER intervention.

ABSTRACTObjective:Chronic heart failure is a disease with high morbidity and symptom burden for patients, and it also places great demands on family members. Patients with heart failure should have access to palliative care for the purpose of improving quality of life for both patients and their families. In the PREFER randomized controlled intervention, patients with New York Heart Association classes III-IV heart failure received person-centered care with a multidisciplinary approach involving collaboration between specialists in palliative and heart failure care. The aim of the present study was to describe family members' experiences of the intervention, which integrated palliative advanced home and heart failure care. METHOD: This study had a qualitative descriptive design based on family member interviews. Altogether, 14 family members participated in semistructured interviews for evaluation after intervention completion. The data were analyzed by means of content analysis. RESULTS: Family members expressed gratitude and happiness after witnessing the patient feeling better due to symptom relief and empowerment. They also felt relieved and less worried, as they were reassured that the patient was being cared for properly and that their own responsibility for care was shared with healthcare professionals. However, some family members also felt as though they were living in the shadow of severe illness, without receiving any support for themselves. SIGNIFICANCE OF RESULTS: Several benefits were found for family members from the PREFER intervention, and our results indicate the significance of integrated palliative advanced home and heart failure care. However, in order to improve this intervention, psychosocial professionals should be included on the intervention team and should contribute by paying closer attention and providing targeted support for family members.

Assessing Optimal Blood Pressure in Patients With Asymptomatic Aortic Valve Stenosis: The Simvastatin Ezetimibe in Aortic Stenosis Study (SEAS).

BACKGROUND: Evidence for treating hypertension in patients with asymptomatic aortic valve stenosis is scarce. We used data from the SEAS trial (Simvastatin Ezetimibe in Aortic Stenosis) to assess what blood pressure (BP) would be optimal. METHODS: A total of 1767 patients with asymptomatic aortic stenosis and no manifest atherosclerotic disease were analyzed. Outcomes were all-cause mortality, cardiovascular death, heart failure, stroke, myocardial infarction, and aortic valve replacement. BP was analyzed in Cox models as the cumulative average of serially measured BP and a time-varying covariate. RESULTS: The incidence of all-cause mortality was highest for average follow-up systolic BP ≥160 mm Hg (4.3 per 100 person-years; 95% confidence interval [CI], 3.1-6.0) and lowest for average systolic BP of 120 to 139 mm Hg (2.0 per 100 person-years; 95% CI, 1.6-2.6). In multivariable analysis, all-cause mortality was associated with average systolic BP <120 mm Hg (hazard ratio [HR], 3.4; 95% CI, 1.9-6.1), diastolic BP ≥90 mm Hg (HR, 1.8; 95% CI, 1.1-2.9), and pulse pressure <50 mm Hg (HR, 1.8; 95% CI, 1.1-2.9), with systolic BP of 120 to 139 mm Hg, diastolic BP of 70 to 79 mm Hg, and pulse pressure of 60 to 69 mm Hg taken as reference. Low systolic and diastolic BPs increased risk in patients with moderate aortic stenosis. With a time-varying systolic BP from 130 to 139 mm Hg used as reference, mortality was increased for systolic BP ≥160 mm Hg (HR, 1.7; P=0.033) and BP of 120 to 129 mm Hg (HR, 1.6; P=0.039). CONCLUSIONS: Optimal BP seems to be systolic BP of 130 to 139 mm Hg and diastolic BP of 70 to 90 mm Hg in these patients with asymptomatic aortic stenosis and no manifest atherosclerotic disease or diabetes mellitus. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00092677.

Decreasing prevalence of abdominal aortic aneurysm and changes in cardiovascular risk factors.

OBJECTIVE: A significant reduction in the incidence of cardiovascular disease, including abdominal aortic aneurysm (AAA), has been observed in the past decades. In this study, a small but geographically well defined and carefully characterized population, previously screened for AAA and risk factors, was re-examined 11 years later. The aim was to study the reduction of AAA prevalence and associated factors. METHODS: All men and women aged 65 to 75 years living in the Norsjö municipality in northern Sweden in January 2010 were invited to an ultrasound examination of the abdominal aorta, registration of body parameters and cardiovascular risk factors, and blood sampling. An AAA was defined as an infrarenal aortic diameter ≥30 mm. Results were compared with a corresponding investigation conducted in 1999 in the same region. RESULTS: A total of 602 subjects were invited, of whom 540 (90%) accepted. In 2010, the AAA prevalence was 5.7% (95% confidence interval [CI], 2.8%-8.5%) among men compared with 16.9% (95% CI, 12.3%-21.6%) in 1999 (P < .001). The corresponding figure for women was 1.1% (95% CI, 0.0%-2.4%) vs 3.5% (95% CI, 1.2%-5.8%; P = .080). A low prevalence of smoking was observed in 2010 as well as in 1999, with only 13% and 10% current smokers, respectively (P = .16). Treatment for hypertension was significantly more common in 2010 (58% vs 44%; P < .001). Statins increased in the population (34% in 2010 vs 3% in 1999; P < .001), and the lipid profile in women had improved significantly between 1999 and 2010. CONCLUSIONS: A highly significant reduction in AAA prevalence was observed during 11 years in Norsjö. Treatment for hypertension and with statins was more frequent, whereas smoking habits remained low. This indicates that smoking is not the only driver behind AAA occurrence and that lifestyle changes and treatment of cardiovascular risk factors may play an equally important role in the observed recent decline in AAA prevalence.

Longitudinal 10-year changes in dietary intake and associations with cardio-metabolic risk factors in the Northern Sweden Health and Disease Study.

BACKGROUND: Dietary risks today constitute the largest proportion of disability-adjusted life years (DALYs) globally and in Sweden. An increasing number of people today consume highly processed foods high in saturated fat, refined sugar and salt and low in dietary fiber, vitamins and minerals. It is important that dietary trends over time are monitored to predict changes in disease risk. METHODS: In total, 15,995 individuals with two visits 10 (±1) years apart in the population-based Västerbotten Intervention Programme 1996-2014 were included. Dietary intake was captured with a 64-item food frequency questionnaire. Percent changes in intake of dietary components, Healthy Diet Score and Dietary Inflammatory Index were calculated and related to body mass index (BMI), serum cholesterol and triglyceride levels and blood pressure at the second visit in multivariable regression analyses. RESULTS: For both sexes, on group level, proportion of energy intake (E%) from carbohydrates and sucrose decreased (largest carbohydrate decrease among 40 year-olds) and E% protein and total fat as well as saturated and poly-unsaturated fatty acids (PUFA) increased (highest protein increase among 30 year-olds and highest fat increase among 60 year-olds) over the 10-year period. Also, E% trans-fatty acids decreased. On individual basis, for both sexes decreases in intake of cholesterol and trans-fatty acids were associated with lower BMI and serum cholesterol at second visit (all P < 0.05). For men, increases in intake of whole grain and Healthy Diet Score were associated with lower BMI and serum cholesterol at second visit (all P < 0.05). Also for men, decreases in intake of trans-fatty acids and increases in Healthy Diet Score were associated with lower systolic blood pressure at second visit (P = 0.002 and P < 0.000). For women, increases in intake of PUFA and Healthy Diet Score were associated with lower BMI at second visit (P = 0.01 and P < 0.05). Surprisingly, increases in intake of sucrose among women were associated with lower BMI at second visit (P = 0.02). CONCLUSIONS: In this large population-based sample, dietary changes over 10 years towards less carbohydrates and more protein and fat were noted. Individual changes towards the Nordic dietary recommendations were associated with healthier cardio-metabolic risk factor profile at second visit.

Higher pulse pressure/stroke volume index is associated with impaired outcome in hypertensive patients with left ventricular hypertrophy the LIFE study.

We tested the prognostic impact of a marker of arterial stiffness, pulse pressure/stroke volume index (PP/SVi), in patients with hypertension and left ventricular (LV) hypertrophy. We used data from 866 patients randomized to losartan or atenolol-based antihypertensive treatment, over a median of 4.8 years, in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. The association of PP/SVi with outcomes was tested in Cox regression analyses and reported as hazard ratio (HR) and 95% confidence intervals (CI). In multivariate regression, reduction of PP/SVi was independently associated with male gender, reduction in systolic blood pressure (BP) and relative wall thickness and with an increase in left ventricular ejection fraction (all p < .05). After adjusting for confounders, higher baseline PP/SVi predicted a 38% higher hazard of combined major fatal and non-fatal cardiovascular events (95% CI 1.04-1.84), and higher hazard of cardiovascular mortality (HR 2.35 (95% CI 1.59-3.48) and stroke (HR 1.45 (95% CI 1.06-1.99) (all p < .05). Higher PP/SVi also predicts higher rate of hospitalization for HF (HR 2.15 (95% CI 1.48-3.12) and a 52% higher hazard of all-cause mortality (95% CI 1.10-2.09) (both p < .05). In hypertensive patients with electrocardiographic LV hypertrophy, higher PP/SVi was associated with increased cardiovascular morbidity and mortality.

Areas for quality improvements in heart failure care: quality of care from the patient's perspective.

BACKGROUND: Heart failure is a serious condition with high mortality and a high symptom burden. Most patients with heart failure will be taken care of in primary care but the knowledge of how the quality of care is perceived by patients with heart failure is limited. OBJECTIVE: The aim was to explore how patients with heart failure report quality of care, in an outpatient setting. METHODS: Seventy-one patients with a confirmed diagnosis of heart failure and who were cared for in an outpatient setting were included in this cross-sectional study. Quality of care was assessed with a short form of the Quality from the Patient's Perspective questionnaire. The items measured four dimensions, and each item consists of both perceived reality of the received care and its subjective importance. RESULTS: Inadequate quality was identified in three out of four dimensions and in items without dimension affiliation. In total, inadequate quality was identified in 19 out of 25 items. Patients reported the highest level of perceived reality in 'my family member was treated well' and the lowest perceived reality in 'effective treatment for loss of appetite'. Effective treatment for shortness of breath was of the highest subjective importance for the patients. CONCLUSION: Important areas for improvement in the quality of care for patients with heart failure in an outpatient setting were identified, such as symptom alleviation, information, participation and access to care.

Can BNP-guided therapy improve health-related quality of life, and do responders to BNP-guided heart failure treatment have improved health-related quality of life? Results from the UPSTEP study.

BACKGROUND: To investigate whether B-type natriuretic peptide (NP)-guided treatment of heart failure (HF) patients improved their health related quality of life (Hr-QoL) compared to routine HF treatment, and whether changes in Hr-QoL differed depending on whether the patient was a responder to NP-guided therapy or not. METHODS: A secondary analysis of the UPSTEP-study, a Scandinavian multicentre study using a prospective, randomized, open, blinded evaluation design on patients with HF with New York Heart Association (NYHA) class II-IV. NP-guiding was aimed to reduce BNP <150 ng/L if < 75 years or BNP < 300 ng/L if > 75 years. A responder was defined as a patient with a BNP < 300 ng/L and/or a decrease in BNP of at least 40% in week 16 compared to study start. Short form-36 (SF-36) was used to measure Hr-QoL. At the study start, 258 patients presented evaluable SF-36 questionnaires, 131 in the BNP group and 127 in the control group. At the study end 100 patients in the NP-guided group and 98 in the control group, presenting data from both the study start and the study end. RESULTS: There were no significant differences in Hr-QoL between NP-guided HF treatment and control group; however significant improvements could be seen in four of the eight domains in the NP-guided group, whereas in the control group improvements could be seen in six of the domains. Among the responders improvements could be noted in four domains whereas in the non-responders improvements could be seen in only one domain evaluating within group changes. CONCLUSIONS: Improved Hr-QoL could be demonstrated in several of the domains in both the NP-guided and the control group. In the responder group within group analyses showed more increased Hr-QoL compared to the non-responder group. However, all groups demonstrated increase in Hr-QoL.

A cost-effectiveness study of person-centered integrated heart failure and palliative home care: Based on a randomized controlled trial.

BACKGROUND: Previous economic studies of person-centered palliative home care have been conducted mainly among patients with cancer. Studies on cost-effectiveness of advanced home care for patients with severe heart failure are lacking when a diagnosis of heart failure is the only main disease as the inclusion criterion. AIM: To assess the cost-effectiveness of a new concept of care called person-centered integrated heart failure and palliative home care. DESIGN: A randomized controlled trial was conducted from January 2011 to 2013 at a center in Sweden. Data collection included cost estimates for health care and the patients' responses to the EQ-5D quality of life instrument. SETTING/PARTICIPANTS: Patients with chronic and severe heart failure were randomly assigned to an intervention (n = 36) or control (n = 36) group. The intervention group received the Palliative Advanced Home Care and Heart Failure Care intervention over 6 months. The control group received the same care that is usually provided by a primary health care center or heart failure clinic at the hospital. RESULTS: EQ-5D data indicated that the intervention resulted in a gain of 0.25 quality-adjusted life years, and cost analysis showed a significant cost reduction with the Palliative Advanced Home Care and Heart Failure Care intervention. Even if costs for staffing are higher than usual care, this is more than made up for by the reduced need for hospital-based care. This intervention made it possible for the county council to use €50,000 for other needs. CONCLUSION: The Palliative Advanced Home Care and Heart Failure Care working mode saves financial resources and should be regarded as very cost-effective.

Increased hsCRP is associated with higher risk of aortic valve replacement in patients with aortic stenosis.

Objective To investigate relations between inflammation and aortic valve stenosis (AS) by measuring high-sensitivity C-reactive protein, at baseline (hsCRP0) and after 1 year (hsCRP1) and exploring associations with aortic valve replacement (AVR). Design We examined 1423 patients from the Simvastatin and Ezetimibe in Aortic Stenosis study. Results During first year of treatment, hsCRP was reduced both in patients later receiving AVR (2.3 [0.9-4.9] to 1.8 [0.8-5.4] mg/l, p < 0.001) and not receiving AVR (1.90 [0.90-4.10] to 1.3 [0.6-2.9] mg/l, p < 0.001). In Cox-regression analyses, hsCRP1 predicted later AVR (HR = 1.17, p < 0.001) independently of hsCRP0 (HR = 0.96, p = 0.33), aortic valve area (AVA) and other risk factors. A higher rate of AVR was observed in the group with high hsCRP0 and an increase during the first year (AVRhighCRP0CRP1inc = 47.3% versus AVRhighCRP0CRP1dec = 27.5%, p < 0.01). The prognostic benefit of a 1-year reduction in hsCRP was larger in patients with high versus low hsCRP0 eliminating the difference in incidence of AVR between high versus low hsCRP0 (AVRhighCRP0CRP1dec = 27.5% versus AVRlowCRP0CRP1dec = 25.8%, p = 0.66) in patients with reduced hsCRP during the first year. Conclusions High hsCRP1 or an increase in hsCRP during the first year of follow-up predicted later AVR independently of AVA, age, gender and other risk factors, although no significant improvement in C-statistics was observed.

Responder to BNP-guided treatment in heart failure. The process of defining a responder.

OBJECTIVES: B-type natriuretic peptide (BNP) levels predict prognosis and outcome in heart failure (HF) patients. To evaluate the optimal cut-off level of BNP to predict death, need for hospitalization, and worsening HF, and also to determine the optimal time to apply the chosen cut-off value. DESIGN: In a sub-study from the Use of PeptideS in Tailoring hEart failure Project or UPSTEP study where tailoring treatment of HF by BNP level was evaluated, we assessed the change in percentage between levels of BNP at study start versus a specific week (2, 6, 10, 16, 24, 36, or 48) during the follow-up period. RESULTS: The optimum cut-off percentage levels were obtained using a Cox proportional regression analysis of death, hospitalization, and worsening HF. A decrease in BNP by less than 40% in week 16 compared with study start and/or a BNP > 300 ng/L presented the highest hazard ratio (HR) for a non-responder to reach a combined endpoint (HR: 2.43; 95% confidence interval or CI: 1.61-3.65; p < 0.00003). This definition gave a 78% risk reduction of cardiovascular (CV) mortality (p > 0.0005) and an 89% risk reduction of HF mortality (p > 0.004), and reduced risk of CV and HF hospitalization for the responders. CONCLUSIONS: Patients with a decrease in BNP of more than 40% compared with that at study start and/or a BNP level below 300 ng/L at week 16 had a significantly reduced risk of CV and HF mortality and hospitalization.

Stroke in patients with aortic stenosis: the Simvastatin and Ezetimibe in Aortic Stenosis study.

BACKGROUND AND PURPOSE: There are limited data on risk stratification of stroke in aortic stenosis. This study examined predictors of stroke in aortic stenosis, the prognostic implications of stroke, and how aortic valve replacement (AVR) with or without concomitant coronary artery bypass grafting influenced the predicted outcomes. METHODS: Patients with mild-to-moderate aortic stenosis enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Diabetes mellitus, known atherosclerotic disease, and oral anticoagulation were exclusion criteria. Ischemic stroke was the primary end point, and poststroke survival a secondary outcome. Cox models treating AVR as a time-varying covariate were adjusted for atrial fibrillation and congestive heart failure, hypertension, age≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years and female sex (CHA2DS2-VASc) scores. RESULTS: One thousand five hundred nine patients were followed for 4.3±0.8 years (6529 patient-years). Rates of stroke were 5.6 versus 21.8 per 1000 patient-years pre- and post-AVR; 429 (28%) underwent AVR and 139 (9%) died. Atrial fibrillation (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.1-6.6), CHA2DS2-VASc score (HR 1.4 per unit; 95% CI, 1.1-1.8), diastolic blood pressure (HR, 1.4 per 10 mm Hg; 95% CI, 1.1-1.8), and AVR with concomitant coronary artery bypass grafting (HR, 3.2; 95% CI, 1.4-7.2, all P≤0.026) were independently associated with stroke. Incident stroke predicted death (HR, 8.1; 95% CI, 4.7-14.0; P<0.001). CONCLUSIONS: In patients with aortic stenosis not prescribed oral anticoagulation, atrial fibrillation, AVR with concomitant coronary artery bypass grafting, and CHA2DS2-VASc score were the major predictors of stroke. Incident stroke was strongly associated with mortality. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00092677.

Impact of isolated systolic hypertension on normalization of left ventricular structure during antihypertensive treatment (the LIFE study).

OBJECTIVE: We tested the impact of isolated systolic hypertension (ISH) on normalization of left ventricular (LV) structure during antihypertensive treatment. METHODS: Baseline and annual echocardiograms were recorded in 873 hypertensive patients with electrocardiographic signs of LV hypertrophy during 4.8 years randomized losartan- or atenolol-based antihypertensive treatment in the Losartan Intervention For Endpoint (LIFE) reduction in hypertension study and classified as having ISH (n = 128) if systolic BP ≥ 160 mmHg and diastolic BP < 90 mmHg, or non-ISH divided into two groups by systolic BP ≥ 160 mmHg (non-ISH ≥ 160 mmHg) (n = 645) and systolic BP < 160 mm Hg (n = 100) (non-ISH < 160 mmHg), respectively. RESULTS: Patients with ISH were older, with higher prevalence of diabetes than non-ISH groups and higher pulse pressure/stroke volume index (all p < 0.05). Baseline systolic blood pressure (BP) differed between groups and was highest in the non-ISH ≥ 160 mmHg group (p < 0.05). Systolic BP reduction was less in the ISH group (p < 0.05). LV geometry did not differ between ISH and non-ISH ≥ 160 mmHg groups at baseline, but ISH had more residual LV hypertrophy of concentric type at the last study visit (p < 0.05). In multivariate analysis, less reduction of LV mass was predicted by ISH (ß = - 0.07) independent of significant associations with baseline LVMi (ß = 0.52) and atenolol-based treatment (ß = - 0.08) and clinical confounders (all p < 0.05). CONCLUSIONS: ISH is associated with impaired normalization of LV mass during systematic antihypertensive treatment. The findings may help explain the higher cardiovascular event rate previously reported in ISH patients.

Effect of Tafamidis on Cardiac Function in Patients With Transthyretin Amyloid Cardiomyopathy: A Post Hoc Analysis of the ATTR-ACT Randomized Clinical Trial.

Importance: Tafamidis has been shown to improve survival in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) compared with placebo. However, its effect on cardiac function has not been fully characterized. Objective: To examine the effect of tafamidis on cardiac function in patients with ATTR-CM. Design, Setting, and Participants: This was an exploratory, post hoc analysis of the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), a multicenter, international, double-blind, placebo-controlled phase 3 randomized clinical trial conducted from December 2013 to February 2018. The ATTR-ACT included 48 sites in 13 counties and enrolled patients aged 18 to 90 years with ATTR-CM. Data were analyzed from July 2018 to September 2023. Intervention: Patients were randomized to tafamidis meglumine, 80 mg or 20 mg, or placebo for 30 months. Main Outcomes and Measures: Patients were categorized based on left ventricular (LV) ejection fraction at enrollment as having heart failure with preserved ejection fraction (≥50%), mildly reduced ejection fraction (41% to 49%), or reduced ejection fraction (≤40%). Changes from baseline to month 30 in LV ejection fraction, LV stroke volume, LV global longitudinal strain, and the ratio of early mitral inflow velocity to septal and lateral early diastolic mitral annular velocity (E/e') were compared in patients receiving tafamidis, 80 mg, vs placebo. Results: A total of 441 patients were randomized in ATTR-ACT, and 436 patients had available echocardiographic data. Of 436 included patients, 393 (90.1%) were male, and the mean (SD) age was 74 (7) years. A total of 220 (50.5%), 119 (27.3%), and 97 (22.2%) had heart failure with preserved, mildly reduced, and reduced LV ejection fraction, respectively. Over 30 months, there was less pronounced worsening in 4 of the echocardiographic measures in patients receiving tafamidis, 80 mg (n = 176), vs placebo (n = 177) (least squares mean difference: LV stroke volume, 7.02 mL; 95% CI, 2.55-11.49; P = .002; LV global longitudinal strain, -1.02%; 95% CI, -1.73 to -0.31; P = .005; septal E/e', -3.11; 95% CI, -5.50 to -0.72; P = .01; lateral E/e', -2.35; 95% CI, -4.01 to -0.69; P = .006). Conclusions and Relevance: Compared with placebo, tafamidis, 80 mg, attenuated the decline of LV systolic and diastolic function over 30 months in patients with ATTR-CM. Approximately half of patients had mildly reduced or reduced LV ejection fraction at enrollment, suggesting that ATTR-CM should be considered as a possible diagnosis in patients with heart failure regardless of underlying LV ejection fraction. Trial Registration: ClinicalTrials.gov Identifier: NCT01994889.

Clinical implications of electrocardiographic left ventricular strain and hypertrophy in asymptomatic patients with aortic stenosis: the Simvastatin and Ezetimibe in Aortic Stenosis study.

BACKGROUND: The prognostic impact of ECG left ventricular strain and left ventricular hypertrophy (LVH) in asymptomatic aortic stenosis is not well described. METHODS AND RESULTS: Data were obtained in asymptomatic patients randomized to simvastatin/ezetimibe combination versus placebo in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Primary end point was the first of myocardial infarction, nonhemorrhagic stroke, heart failure, aortic valve replacement, or cardiovascular death. The predictive value of ECG left ventricular strain (defined as T-wave inversion in leads V(4) through V(6)) and LVH, assessed by Sokolow-Lyon voltage criteria (R(V5-6)+S(V1) ≥35 mV) and Cornell voltage-duration criteria {[RaVL+S(V3)+(6 mV in women)]×QRS duration ≥2440 mV · ms}, was evaluated by adjustment for other prognostic covariates. A total of 1533 patients were followed for 4.3±0.8 years (6592 patient-years of follow-up), and 627 cardiovascular events occurred. ECG strain was present in 340 patients (23.6%), with LVH by Sokolow-Lyon voltage in 260 (17.1%) and by Cornell voltage-duration product in 220 (14.6%). In multivariable analyses, ECG left ventricular strain was associated with 3.1-fold higher risk of in-study myocardial infarction (95% confidence interval, 1.4-6.8; P=0.004). Similarly, ECG LVH by both criteria predicted, compared with no ECG LVH, 5.8-fold higher risk of heart failure (95% confidence interval, 2.0-16.8), 2.0-fold higher risk of aortic valve replacement (95% confidence interval, 1.3-3.1; both P=0.001), and 2.5-fold higher risk of a combined end point of myocardial infarction, heart failure, or cardiovascular death (95% confidence interval, 1.3-4.9; P=0.008). CONCLUSIONS: ECG left ventricular strain and LVH were independently predictive of poor prognosis in patients with asymptomatic aortic stenosis. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00092677.

Accuracy of death certificates of cardiovascular disease in a community intervention in Sweden.

AIM: The aim was to investigate the possibility to evaluate the mortality pattern in a community intervention programme against cardiovascular disease by official death certificates. METHODS: For all deceased in the intervention area (Norsjö), the accuracy of the official death certificates were compared with matched controls in the rest of Västerbotten. The official causes of death were compared with new certificates, based on the last clinical record, issued by three of the authors, and coded by one of the authors, all four accordingly blinded. RESULTS: The degree of agreement between the official underlying causes of death in "cardiovascular disease" (CVD) and the re-evaluated certificates was not found to differ between Norsjö and the rest of Västerbotten. The agreement was 87% and 88% at chapter level, respectively, but only 55% and 55% at 4-digit level, respectively. The reclassification resulted in a 1% decrease of "cardiovascular deaths" in both Norsjö and the rest of Västerbotten. CONCLUSIONS: The disagreements in the reclassification of cause of death were equal but large in both directions. The official death certificates should be used with caution to evaluate CVD in small community intervention programmes, and restricted to the chapter level and total populations.