Acute adverse events of Sars-CoV2 vaccines: Experiences from a health care worker vaccination campaign in two municipal hospitals in northwest Germany.

Vaccination is considered the best measure to overcome the Sars-Cov2 pandemic. However, changing national recommendations on sequence and time frame necessitate the collection of real-word data on adverse events of Sars-CoV2 vaccination protocols outside of pivotal trials. We report results from a survey on the adverse events and the operational consequences of a Sars-CoV2 vaccination campaign with partly mixed vaccination protocol as well as booster vaccination. While the spectrum of adverse effects in our cohort appeared to be similar to pivotal studies, there were substantial differences in both frequency and distribution with only 3 out of 10 participants staying symptom-free. In over 26% of vaccinees symptoms were so severe, that they stayed at home with mean days on sick leave being 1.5 per person using mixed vaccination protocol. Being aware, that these results might partially be attributable to nocebo effects they are of importance for future vaccination campaigns.

Morbidity and mortality in patients with cardiovascular risk factors and obstructive sleep apnoea: results from the DIAST-CHF cohort.

STUDY OBJECTIVES: Aim of the study was to investigate the association between obstructive sleep apnoea (OSA) and cardiovascular morbidity and mortality in a cohort of patients with cardiovascular risk factors. METHODS: In this prospective study, 378 patients of the DIAST-CHF cohort were screened for OSA by home polygraphy. Inclusion criteria were risk factors for diastolic heart failure, such as hypertension, diabetes mellitus, atherosclerotic disease, or history of chronic heart failure. Patients were followed up after 1, 2, 5, 9 and 10 years for the occurrence of major adverse cardiac and cerebrovascular events (MACE and MACCE). RESULTS: 344 patients were included in the analysis, of which 60% were diagnosed with OSA (apnoea-hypopnoea index ≥5/h). Overall mortality was higher in the OSA group (14.9% vs. 5.9%; p = 0.007), but significance disappeared after adjustment for age and sex (hazard ratio (HR) 1.89, 95% confidence interval (CI) 0.86-4.16, p = 0.12). There was no significant difference in the occurrence of MACE or MACCE in patients with OSA compared to those without OSA (MACE: 31% vs. 30%; p = 0.61; MACCE: 32% vs. 30%; p = 0.53). CONCLUSION: We did not find evidence of an adverse effect of OSA on cardiovascular morbidity and mortality in a cohort of patients with cardiovascular risk factors.

Prognostic impact of diastolic dysfunction in systolic heart failure-A cross-project analysis from the German Competence Network Heart Failure.

BACKGROUND: We investigated the modifying role and prognostic importance of diastolic dysfunction (DD) in patients with heart failure and systolic dysfunction (SD). HYPOTHESIS: The echocardiographic evaluation of diastolic function in patients with SD provides further prognostic information. METHODS: From the German Competence Network Heart Failure, 1046 heart failure patients with reduced left ventricular ejection fraction (LVEF; <50%) were echocardiographically studied and followed for a median of 5 years. SD was subdivided into nonsevere (LVEF 36%-49%) and severe (LVEF ≤35%); DD was subdivided into nonsevere (E/E' <15) and severe (E/E' ≥15). RESULTS: In general, severe SD was associated with higher hazard ratios (HRs; 2-fold to 3.5-fold) for all endpoints (all-cause death, cardiac death, cardiovascular hospitalization, duration of hospitalization). Patients with severe SD had a 2.5-fold risk of death (95% confidence interval [CI]: 1.84-3.47, P < 0.001), and patients with severe DD showed a 1.8-fold risk (95% CI: 1.17-2.61, P = 0.004). Furthermore, we observed a strong interaction of SD and DD: concomitant severe DD in patients with moderate SD increased risk substantially (HR: 1.73, 95% CI: 1.16-2.6, P = 0.007); by contrast, in patients with severe SD, additional presence of severe DD added little or no risk (HR for interaction: 0.5-1.2). CONCLUSIONS: In heart failure patients with reduced LVEF, the evaluation of diastolic function provides additional prognostic information. Although severe SD generally increased the risk for all endpoints, the degree of DD and its impact as a prognostic marker for overall and cardiovascular mortality appeared of particular relevance in subjects with nonsevere SD.

Arterial stiffness and elevated left ventricular filling pressure in patients at risk for the development or a previous diagnosis of HF-A subgroup analysis from the DIAST-CHF study.

Left ventricular filling pressure (LVFP) is a marker for diastolic dysfunction and heart failure (HF) with preserved ejection fraction (pEF). The interaction between arterial stiffness (AS) and elevated LVFP has not been sufficiently investigated. In 257 patients with preserved left ventricular ejection fraction (mean age: 66 years, 53% female, mean left ventricular ejection fraction: 61%) and at least one cardiovascular risk factor (eg, hypertension and diabetes) for the development of HF or a previous diagnosis of HF, LVFP was estimated in accordance with the recommendations of the American Society of Echocardiography (elevated when E/e' ≥ 13, left atrial volume index ≥ 34 mL/m2). LVFP was correlated with radial pulse wave analysis (augmentation index normalized by 75 b/min [AIx@75]) and carotid-femoral pulse wave velocity (cfPWV). Thirty-eight percent of patients demonstrated an elevated LVFP. These patients were significantly older (68.3 ± 7.4 vs. 63.5 ± 7.6 years, P < .001), demonstrated a higher body mass index (29.8 ± 4.6 vs. 28.0 ± 5.0; P < .01), presented more often with hypertension (89.7% vs. 73.1%, P < .01), hypercholesterolemia (32.0% vs. 21.3%, P < .05), dyspnea on exertion (28.4% vs. 16.6%, P < .05), and peripheral edema (25.3% vs. 10.2%, P < .01). cfPWV and AIx@75 and were significantly elevated in patients with elevated LVFP (12.2 ± 2.7 m/s vs. 10.5 ± 2.6 m/s, P < .001, an 29.2 ± 6.7% vs. 27.4 ± 6.7%, P < .05 respectively). cfPWV and AIx@75 were correlated with echocardiographic parameters, that is, posterior wall thickness (r = 0.292, P < .001; r = 0.167, P < .01), left ventricular mass index (r = 0.255, P < .001; r = -0.192, P < .01), e' (r = -0.508, P < .001; r = -0.159, P < .05), and E/e' (r = 0.380, P < .001; r = 0.200, P < .01). cfPWV correlated with left atrial volume index (r = 0.189, P < .05) and increasing E/A ratio (r = -0.334, P < .001). Multivariate linear regression analysis demonstrated age and PWV as most important and independent predictors of LVFP elevation in the cohort. Increased AS measured by cfPWV was associated with an elevated LVFP in patients with preserved systolic function. Whether targeting AS as a major component of diastolic dysfunction and HF with preserved ejection fraction needs to be further investigated.

Influence of different aetiologies on clinical course and outcome in patients with dilated cardiomyopathy.

BACKGROUND: The clinical phenotype dilated cardiomyopathy is assumed to be the endstage of a multifactorial aetiopathogenetic pathophysiology which includes a not satisfactorily defined group of patients with inflammatory cardiomyopathy. METHODS: Within the German Competence Network Heart Failure patients with heart failure due to dilated cardiomyopathy of viral/inflammatory (DCMi/v) and nonviral/noninflammatory (DCM) aetiology were enrolled. After 1 year 237 patients (180 male/57 female) were re-examined including complete clinical work-up. The association of different clinical courses with the time from initial diagnosis of heart failure (newly: ≤ 1 year; late: > 1 year) was investigated. RESULTS: After 1-year-follow-up New York Heart Association (NYHA) class (by -0.48 in newly diagnosed DCM and -0.82 in newly diagnosed DCMi/v in addition to -0.24 in late diagnosed DCM and -0.17 in late diagnosed DCMi/v) as well as left ventricular ejection fraction (+14% in newly diagnosed DCM and DCMi/v and +6% in later diagnosed DCM and DCMi/v) were significantly improved in all patients. In patients with early diagnosed dilated cardiomyopathy a strong improvement of NYHA class could be demonstrated. CONCLUSIONS: This study demonstrates for the first time a significant interaction between duration of disease, NYHA class and left ventricular ejection fraction in patients with DCM. Our results clearly demonstrate that in patients with DCM an early diagnosis within 1 year after occurrence of clinical signs is associated with a strong improvement in the clinical course, whereas late diagnosis results in a loss of change in clinical course and outcome.

Use of drug-eluting stents in acute myocardial infarction with persistent ST-segment elevation: results of the ALKK PCI-registry.

BACKGROUND: Drug-eluting stents (DES) reduce the rate of in-stent restenosis (ISR) and target vessel revascularization significantly when compared with bare metal stents (BMS). Their beneficial effects have been demonstrated in patients with acute myocardial infarction also, but the use of DES in the latter population seems to be still limited in clinical practice. METHODS AND RESULTS: From January 2006 to December 2011, 25,424 patients with ST-elevation myocardial infarction were enrolled in the German ALKK PCI-registry. In 5,467 patients (21.5 %), a DES was implanted in the culprit segment, in 16,911 patients (66.5 %) a BMS, and 2,959 patients (11.6 %) received neither DES nor BMS. The rates of DES for typical subgroups were 31.7 % in patients with diabetes, 36.6 % in unprotected left main stenosis, 32.4 % in ostial lesions, 32.0 % for a stent length >15 mm, 26.2 % for a stent diameter ≤3 mm, and 58.5 % for ISR. There was a wide range in the use of DES between the different ALKK hospitals with a minimum of 2.3 % and a maximum of 58.3 % for the total study period (median 22.0 %, quartiles 14.6 and 37.5 %). CONCLUSIONS: Despite convincing data for the use of DES in patients with STEMI, there is still an underuse of DES in this clinical setting in Germany. This is particularly worrying for the subgroups of patients and lesions with a high risk of restenosis. Further efforts are needed to reduce the skepticism about DES and to improve guideline adherent treatment.

NT-proANP and NT-proBNP as prognostic markers in patients with acute decompensated heart failure of different etiologies.

BACKGROUND AND PURPOSE: Peak NT-proANP and NT-proBNP plasma levels after hospital admission may be of additional prognostic value in patients with acute decompensation of heart failure. The time-course of natriuretic plasma levels after hospital admission, and a possible influence of the underlying etiology on the time-course have not been sufficiently investigated. METHODS AND RESULTS: Natriuretic peptide plasma levels of 85 patients with decompensated heart failure from ischemic and non-ischemic origins were measured at baseline and at 12h after hospital admission. NT-proBNP plasma levels on admission were lower compared to 12-hour-plasma levels, whereas NT-proANP plasma levels on admission were higher compared to 12-hour-plasma levels. Twenty-six patients (31%) died within the first 30 days. In patients who died within the first 30 days after admission NT-proANP and NT-proBNP plasma levels on admission and 12h later were significantly higher compared to survivors. Irrespective of different etiologies NT-proANP on admission and NT-proBNP 12h after admission were highest and demonstrated superior impact with respect to the prediction of 30-day-mortality. CONCLUSIONS: NT-proANP and NT-proBNP are powerful markers of 30-day-mortality in patients with acute heart failure of ischemic and non-ischemic origins. With respect to the prediction of 30-day-mortality, NT-proBNP plasma levels at 12h after admission are comparable with NT-proANP plasma levels on admission. These data underline the fact that with regard to etiology-dependent hemodynamic changes and plasma half-time, the determination of peak plasma levels is of highest importance for the estimation of the impact of natriuretic peptides on the prognosis of patients with decompensated heart failure.

Impact of obstructive sleep apnoea on diastolic function.

We investigated whether obstructive sleep apnoea (OSA) independently affects diastolic function in a primary care cohort of patients with cardiovascular risk factors. 378 study participants with risk factors for diastolic dysfunction were prospectively included and a polygraphy was performed in all patients. Diastolic dysfunction was assessed by comprehensive echocardiography including tissue Doppler. Sleep apnoea was classified according to apnoea/hypopnoea index (AHI) as none (AHI <5 events·h(-1)), mild (AHI ≤5 to <15 events·h(-1)) or moderate-to-severe (AHI ≥15 events·h(-1)). Patients with central sleep apnoea (n=14) and patients with previously diagnosed sleep apnoea (n=12) were excluded. In the remaining 352 subjects, 21.6% had an AHI ≥15 events·h(-1). The prevalence of diastolic dysfunction increased with the severity of sleep apnoea from 44.8% (none) to 56.8% (mild) to 69.7% (moderate-to-severe sleep apnoea) (p=0.002). The degree of diastolic dysfunction also increased with sleep apnoea severity (p=0.004). In univariate regression analysis, age, desaturation index, AHI, cardiac frequency, angiotensin receptor 1 antagonist therapy, body mass index (BMI) and left ventricular mass were associated with diastolic dysfunction. In multivariate regression analysis, only age, BMI, AHI and cardiac frequency were independently associated with diastolic dysfunction. Moderate-to-severe OSA is independently associated with diastolic dysfunction in patients with classical risk factors for diastolic dysfunction.

Serum levels of interleukin-6 and interleukin-10 in relation to depression scores in patients with cardiovascular risk factors.

It is currently unknown whether elevated cytokine levels in depression are confined to any specific subgroup of depressive patients. In this study, medical out-patients presenting with cardiovascular risk factors (N = 356) were assessed for both cognitive-affective and physical symptoms of depression using the Hospital Anxiety and Depression Scale (HADS) and the Maastricht questionnaire (MQ), respectively. In study participants assigned to the highest (≥21) and lowest (≤5) quartile for the MQ score, serum levels of cytokines were measured. We found highly significant associations between cognitive-affective symptoms of depression and elevated serum levels of interleukin-6 (IL-6; ρ = .231; p = .002) and interleukin-10 (IL-10; ρ = .370; p < .001), respectively. In multiple regression models elevated IL-10 serum concentration was independently related to cognitive-affective symptoms of depression (ρ = .165; p = .002). When all cytokines were included in one model, elevated IL-10 serum concentrations remained a significant predictor for depressive mood (ρ = .157; p = .009). In patients with cardiovascular risk factors and extreme scores for vital exhaustion, elevated serum IL-6 and even more IL-10 concentrations are linked to the presence of depressive mood. Future studies will have to test whether the so far unreported association of IL-10 with depressive mood represents a causal pathway involved in the pathogenesis or in the prognostic effect of depressive mood in cardiac patients.

Heart failure therapy in diabetic patients-comparison with the recent ESC/EASD guideline.

BACKGROUND: To assess heart failure therapies in diabetic patients with preserved as compared to impaired systolic ventricular function. METHODS: 3304 patients with heart failure from 9 different studies were included (mean age 63 ± 14 years); out of these, 711 subjects had preserved left ventricular ejection fraction (≥ 50%) and 994 patients in the whole cohort suffered from diabetes. RESULTS: The majority (>90%) of heart failure patients with reduced ejection fraction (SHF) and diabetes were treated with an ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB) or with beta-blockers. By contrast, patients with diabetes and preserved ejection fraction (HFNEF) were less likely to receive these substance classes (p < 0.001) and had a worse blood pressure control (p < 0.001). In comparison to patients without diabetes, the probability to receive these therapies was increased in diabetic HFNEF patients (p < 0.001), but not in diabetic SHF patients. Aldosterone receptor blockers were given more often to diabetic patients with reduced ejection fraction (p < 0.001), and the presence and severity of diabetes decreased the probability to receive this substance class, irrespective of renal function. CONCLUSIONS: Diabetic patients with HFNEF received less heart failure medication and showed a poorer control of blood pressure as compared to diabetic patients with SHF. SHF patients with diabetes were less likely to receive aldosterone receptor blocker therapy, irrespective of renal function.

The novel biomarker growth differentiation factor 15 in heart failure with normal ejection fraction.

AIMS: Heart failure with normal ejection fraction (HFnEF) is an important clinical entity that remains incompletely understood. The novel biomarker growth differentiation factor 15 (GDF-15) is elevated in systolic heart failure (HFrEF) and is predictive of an adverse outcome. We investigated the clinical relevance of GDF-15 plasma levels in HFnEF. METHODS AND RESULTS: A subgroup of patients from the ongoing DIAST-CHF observational trial, with a history of chronic heart failure (CHF) or positive Framingham criteria at presentation, was selected. Patients were classified as having either HFrEF (n=86) or HFnEF (n=142) and compared with healthy elderly controls (n=188) from the same cohort. Growth differentiation factor 15 levels in HFnEF were significantly higher than in controls and similar to those in HFrEF. In multivariate analysis, factors significantly associated with GDF-15 levels were age, sex, estimated glomerular filtration rate (eGFR), presence of HFrEF and HFnEF. Growth differentiation factor 15 correlated with multiple echocardiographic markers of diastolic function and was associated with 6 min walk test performance and SF-36 physical score on multivariate analysis in all patients. When using a classification for HFnEF that did not employ N-terminal pro brain natriuretic peptide (NT-proBNP) as a diagnostic criterion, the diagnostic properties of GDF-15 for detecting HFnEF tended to be superior to those of NT-proBNP, and a combination significantly improved diagnostic accuracy. CONCLUSION: Growth differentiation factor 15 is elevated in HFnEF to a similar degree as in HFrEF. It is independently associated with impairment in exercise capacity and in physical components of quality of life. Diagnostic precision of GDF-15 is at least as good as that of NT-proBNP and combining both markers improves diagnostic accuracy.

[Importance of surfactant proteins B and D for the differential diagnosis of acute dyspnea]. / Bedeutung der Surfactant-Proteine B und D in der Differentialdiagnostik der akuten Dyspnoe.

BACKGROUND AND PURPOSE: The basis for an optimal therapy of cardiopulmonary diseases is the assessment of an early diagnosis. This implies an evaluation of possible differential diagnoses of acute dyspnea. In numerous studies, natriuretic peptides were characterized as additional, meaningful parameters for the assessment of left ventricular function. Current studies could demonstrate that surfactant proteins B (SP-B) and D (SP-D) are of importance for the differentiation of patients with acute dyspnea. The aim of this study was to compare the values of NT-proBNP (N-terminal brain natriuretic peptide) and surfactant proteins for the assessment of a final diagnosis in patients with acute dyspnea. PATIENTS AND METHODS: NT-proBNP, SP-B and SP-D were measured in 81 patients with acute dyspnea in the emergency room and were correlated with clinical and echocardiographic parameters with respect to the final diagnosis. For this, patients were classified with respect to clinical and echocardiographic parameters in different subgroups concerning the final diagnosis of acute dyspnea. RESULTS: In patients with a cardiac origin of acute dyspnea, plasma levels of NT-proBNP were significantly higher as compared to patients with a noncardiac diagnosis (p = 0.04). SP-D was highest in patients with a cardiac origin of acute dyspnea, but after performing regression analysis it seems to be of less importance for the differential diagnosis of acute dyspnea as compared to NT-proBNP. SP-B plasma levels were not different between the four subgroups. CONCLUSION: NT-proBNP is of importance for the differential diagnosis of acute dyspnea. Although SP-D shows similar changes of plasma levels between the four subgroups, it seems to be of less importance for the differential diagnosis of acute dysnea. SP-B occurs to be of no relevance for the differentiation between cardiac and noncardiac origin of acute dyspnea.

Elevated serum levels of interleukin-10 and tumor necrosis factor α [corrected] are both associated with vital exhaustion in patients with cardiovascular risk factors.

BACKGROUND: Vital exhaustion, a psychological state characterized by unusual fatigue, irritability, and feelings of demoralization, has been identified as a risk factor for cardiovascular diseases and linked to elevated levels of pro-inflammatory cytokines. OBJECTIVE: The purpose of this study was to investigate the relationship between vital exhaustion and cytokine levels in patients with cardiovascular risk factors. METHOD: The entire cohort consisted of 356 primary-care patients with cardiovascular risk factors who participated in a study of early recognition of heart failure. All participants completed the Maastricht questionnaire (MQ) for assessing vital exhaustion. Cytokine serum levels were measured in all those subjects (N=178) who were assigned to the highest and lowest quartiles of the MQ, respectively. RESULTS: We found that elevated serum concentrations of IL-6, TNFα, and IL-10, but not IL-1ß or natriuretic peptides were associated with high MQ scores indicative of vital exhaustion. Using logistic regression analyses controlling for clinical variables and Type D personality, both TNFα (multivariate odds ratio [OR] =1.86; 95%-confidence interval [CI] =1.30-2.68; p=0.001) and IL-10(OR=1.62; 95%-CI=1.15-2.28; p=0.006), but not other cytokines significantly predicted vital exhaustion independently of other clinical and laboratory parameters examined [corrected]. CONCLUSION: The subjective state of vital exhaustion is linked to a substantial alteration in the pattern of secreted cytokines. Data suggest that a disturbance in the levels of both pro-inflammatory and anti-inflammatory mediators, rather than isolated stimulation by pro-inflammatory cytokines, is associated with the mental and physical changes of vital exhaustion.

Natriuretic peptides in the detection of preclinical diastolic or systolic dysfunction.

AIMS: The diagnostic value of natriuretic peptides in asymptomatic patients at risk for diastolic or systolic HF is controversial. We tested (1) the prevalence of preclinical LV dysfunction in an at-risk cohort; (2) the diagnostic accuracy of natriuretic peptides alone or in combination with clinical parameters for predicting asymptomatic left ventricular systolic or diastolic dysfunction. METHODS: 542 primary care patients (mean age 63 +/- 11 years, 42% female) without prediagnosed HF, but with risk factors for left ventricular dysfunction, underwent thorough cardiological workup, including echocardiography and analysis of natriuretic peptides. RESULTS: 23 patients (4%) showed reduced systolic function (EF < 50%), and 15 patients (3%) had severe diastolic dysfunction. All natriuretic peptides significantly increased with decreasing ejection fraction and with increasing degree of diastolic dysfunction. For natriuretic peptides, receiver operating characteristics analysis yielded good results for the detection of systolic dysfunction or severe diastolic dysfunction. Combining clinical parameters with natriuretic peptide data improved the diagnostic accuracy and largely reduced the number of needed screening echoes to identify patients with LV systolic or diastolic dysfunction. CONCLUSIONS: The prevalence of preclinical diastolic dysfunction is high in primary care patients at risk, but the relative prevalence of severe diastolic dysfunction and systolic dysfunction is only 7%. High-risk individuals may be screened most efficiently by using a score system incorporating clinical data and NT-proBNP.

Association of Cheyne-Stokes respiration and cardiac cachexia in congestive heart failure.

In patients with congestive heart failure (CHF) cachexia as well as Cheyne-Stokes respiration (CSR) are well known disorders. The relationship between CSR and cardiac cachexia however, remains unclear so far. Clinical as well as full-night polysomnographic data from 12 cachectic patients were compared to 13 non-cachectic patients with CHF. The non-cachectic patients did not differ significantly in age (57.3+/-11.6 vs 64.8+/-14.5 years), body mass index (26.4+/-4.0 vs 25.2+/-3.2 kg m-(2)) or ejection fraction (21.8+/-5 vs 23.3+/-7%) from cachectic patients. The weight loss was 2.1+/-2.3 kg in non-cachectic vs 11.5+/-2.7 kg in cachectic patients (p<0.0001). A significant difference was detected for the prevalence CSR (5 vs 10 patients, p<0.03). In this study a high prevalence of sleep breathing disorders, in particular of CSR in CHF patients with cachexia was detected.

Blunted frequency-dependent upregulation of cardiac output is related to impaired relaxation in diastolic heart failure.

AIMS: We tested the hypothesis that, in heart failure with normal ejection fraction (HFNEF), diastolic dysfunction is accentuated at increasing heart rates, and this contributes to impaired frequency-dependent augmentation of cardiac output. METHODS AND RESULTS: In 17 patients with HFNEF (median age 69 years, 13 female) and seven age-matched control patients, systolic and diastolic function was analysed by pressure-volume loops at baseline heart rate and during atrial pacing to 100 and 120 min(-1). At baseline, relaxation was prolonged and end-diastolic left ventricular stiffness was higher in HFNEF, whereas all parameters of systolic function were not different from control patients. This resulted in smaller end-diastolic volumes, higher end-diastolic pressure, and a lower stroke volume and cardiac index in HFNEF vs. control patients. During pacing, frequency-dependent upregulation of contractility indices (+dP/dt(max) and Ees) occurred similarly in HFNEF and control patients, but frequency-dependent acceleration of relaxation (dP/dt(min)) was blunted in HFNEF. In HFNEF, end-diastolic volume and stroke volume decreased with higher heart rates while both remained unchanged in control patients. CONCLUSION: In HFNEF, frequency-dependent upregulation of cardiac output is blunted. This results from progressive volume unloading of the left ventricle due to limited relaxation reserve in combination with increased LV passive stiffness, despite preserved force-frequency relation.

Natriuretic peptide vs. clinical information for diagnosis of left ventricular systolic dysfunction in primary care.

BACKGROUND: Screening of primary care patients at risk for left ventricular systolic dysfunction by a simple blood-test might reduce referral rates for echocardiography. Whether or not natriuretic peptide testing is a useful and cost-effective diagnostic instrument in primary care settings, however, is still a matter of debate. METHODS: N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, clinical information, and echocardiographic data of left ventricular systolic function were collected in 542 family practice patients with at least one cardiovascular risk factor. We determined the diagnostic power of the NT-proBNP assessment in ruling out left ventricular systolic dysfunction and compared it to a risk score derived from a logistic regression model of easily acquired clinical information. RESULTS: 23 of 542 patients showed left ventricular systolic dysfunction. Both NT-proBNP and the clinical risk score consisting of dyspnea at exertion and ankle swelling, coronary artery disease and diuretic treatment showed excellent diagnostic power for ruling out left ventricular systolic dysfunction. AUC of NT-proBNP was 0.83 (95% CI, 0.75 to 0.92) with a sensitivity of 0.91 (95% CI, 0.71 to 0.98) and a specificity of 0.46 (95% CI, 0.41 to 0.50). AUC of the clinical risk score was 0.85 (95% CI, 0.79 to 0.91) with a sensitivity of 0.91 (95% CI, 0.71 to 0.98) and a specificity of 0.64 (95% CI, 0.59 to 0.67). 148 misclassifications using NT-proBNP and 55 using the clinical risk score revealed a significant difference (McNemar test; p < 0.001) that was based on the higher specificity of the clinical risk score. CONCLUSION: The evaluation of clinical information is at least as effective as NT-proBNP testing in ruling out left ventricular systolic dysfunction in family practice patients at risk. If these results are confirmed in larger cohorts and in different samples, family physicians should be encouraged to rely on the diagnostic power of the clinical information from their patients.

Impact of diabetes on left ventricular diastolic function in patients with arterial hypertension.

AIMS: To analyse the effect of diabetes (DM) on diastolic function in hypertensive patients. METHODS: 439 hypertensive patients were selected for participation in this study. All participants had an echocardiographic evaluation of systolic and diastolic function. The overall degree of diastolic function and specific parameters (e.g. E/Ea ratio) were analysed. RESULTS: We divided the cohort (63+/-10 years) into those with diabetes mellitus (DM(+), n=124) and without diabetes mellitus (DM(-), n=315). The prevalence of normal diastolic function was lower in DM(+) than DM(-) (19.4% vs. 30.8%); mild (65.3% vs. 60.0%) and moderate/ severe diastolic dysfunction were more frequent in DM(+) (15.3% vs. 9.2%, p=0.022). The E/Ea ratio, an estimate of left ventricular end-diastolic pressure, was significantly higher in DM(+) (12.3+/-4.4) as compared to DM(-) (10.8+/-3.6, p<0.001). Sex-specific analysis revealed that the effect of DM on diastolic function was mainly limited to the male subgroup. Multivariate logistic regression analysis showed that diabetes affected diastolic function in males independent of blood pressure, left ventricular mass index, concomitant medication and prevalence of coronary artery disease. CONCLUSION: Diabetes negatively affects diastolic function in patients with arterial hypertension. This effect is mainly confined to the male subgroup.

Stretch-dependent modulation of [Na+]i, [Ca2+]i, and pHi in rabbit myocardium--a mechanism for the slow force response.

OBJECTIVE: Rabbit ventricular myocardium is characterized by a biphasic response to stretch with an initial, rapid increase in force followed by a delayed, slow increase in force (slow force response, SFR). The initial phase is attributed to increased myofilament Ca(2+) sensitivity, but the mechanisms of the delayed phase are only incompletely understood. We tested whether stretch-dependent stimulation of Na(+)/H(+) exchange (NHE1) and consecutive changes in pH(i) and/or [Na(+)](i) may underlie the SFR. METHODS: Isometric contractions of rabbit ventricular muscles were recorded in bicarbonate-containing Tyrode's (Tyrode) or bicarbonate-free HEPES-buffered solution (HEPES). Muscles were loaded with the Ca(2+) indicator aequorin, the pH indicator BCECF, or the Na(+) indicator SBFI and rapidly stretched from 88% (L(88)) to 98% (L(98)) of optimal length. The resulting immediate and slow increases in twitch force (1st phase and SFR) as well as changes in [Ca(2+)](i), [Na(+)](i), or pH(i) were quantified before and after inhibition of NHE1 by HOE 642 (3 microM) or reverse-mode Na(+)/Ca(2+) exchange (NCX) by KB-R 7943 (5 microM). RESULTS: In both Tyrode (n=21) and HEPES (n=22), developed force increased to approximately 160% during the 1st phase followed by a further increase to approximately 205% during the SFR. The SFR was accompanied by a 21% increase of the aequorin light transient (n=4; normalized to the 1st phase) and a approximately 3 mM increase in [Na(+)](i) (n=4-7). The SFR was also associated with an increase in pH(i). However, this increase was delayed and was significant only after the SFR had reached its maximum. The delayed pH(i) increase was larger in HEPES than in Tyrode. HOE 642 and/or KB-R 7943 reduced the SFR by approximately 30-40%. In addition, HOE 642 diminished the stretch-mediated elevation of [Na(+)](i) by 72% and the delayed alkalinization. CONCLUSIONS: The data are consistent with the hypothesis that SFR results from increases in [Ca(2+)](i) secondary to altered flux via NCX in part resulting from increases in [Na(+)](i) mediated by NHE1.

Functional relevance of the stretch-dependent slow force response in failing human myocardium.

Stretch induces immediate and delayed inotropic effects in mammalian myocardium via distinct mechanosensitive pathways, but these effects are poorly characterized in human cardiac muscle. We tested the effects of stretch on immediate and delayed force response in failing human myocardium. Experiments were performed in muscle strips from 52 failing human hearts (37 degrees C, 1 Hz, bicarbonate buffer). Muscles were stretched from 88% of optimal length to 98% of optimal length. The resulting immediate and delayed (ie, slow force response [SFR]) increases in twitch force were assessed without and after blockade of the sarcoplasmic reticulum (SR; cyclopiazonic acid and ryanodine), stretch-activated ion channels (SACs; gadolinium, streptomycin), L-type Ca2+-channels (diltiazem), angiotensin II type-1 (AT1) receptors (candesartan), endothelin (ET) receptors (PD145065 or BQ123), Na+/H+ exchange (NHE1; HOE642), or reverse-mode Na+/Ca+ exchange (NCX; KB-R7493). We also tested the effects of stretch on SR Ca2+ load (rapid cooling contractures [RCCs]) and intracellular pH (in BCECF-loaded trabeculae). Stretch induced an immediate (<10 beats), followed by a slow (5 to 10 minutes), force response. Twitch force increased to 232+/-6% of prestretch value during the immediate phase, followed by a further increase to 279+/-8% during the SFR. RCC amplitude significantly increased, but pHi did not change during SFR. Inhibition of SACs, L-type Ca2+ channels, AT1 receptors, or ET receptors did not affect the stretch-dependent immediate or SFR. In contrast, the SFR was reduced by NHE1 inhibition and almost completely abolished by reverse-mode NCX inhibition or blockade of sarcoplasmic reticulum function. The data demonstrate the existence of a functionally relevant, SR-Ca2+-dependent SFR in failing human myocardium, which partly depends on NHE1 and reverse-mode NCX activation.