Biomarkers in outpatient heart failure management; Are they correlated to and do they influence clinical judgment?

AIMS: Heart failure (HF) management is complicated by difficulties in clinical assessment. Biomarkers may help guide HF management, but the correspondence between clinical evaluation and biomarker serum levels has hardly been studied. We investigated the correlation between biomarkers and clinical signs and symptoms, the influence of patient characteristics and comorbidities on New York Heart Association (NYHA) classification and the effect of using biomarkers on clinical evaluation. METHODS AND RESULTS: This post-hoc analysis comprised 622 patients (77 ± 8 years, 76 % NYHA class ≥3, 80 % LVEF ≤45 %) participating in TIME-CHF, randomising patients to either NT-proBNP-guided or symptom-guided therapy. Biomarker measurements and clinical evaluation were performed at baseline and after 1, 3, 6, 12 and 18 months. NT-proBNP, GDF-15, hs-TnT and to a lesser extent hs-CRP and cystatin-C were weakly correlated to NYHA, oedema, jugular vein distension and orthopnoea (ρ-range: 0.12-0.33; p < 0.01). NT-proBNP correlated more strongly to NYHA class in the NT-proBNP-guided group compared with the symptom-guided group. NYHA class was significantly influenced by age, body mass index, anaemia, and the presence of two or more comorbidities. CONCLUSION: In HF, biomarkers correlate only weakly with clinical signs and symptoms. NYHA classification is influenced by several comorbidities and patient characteristics. Clinical judgement seems to be influenced by a clinician's awareness of NT-proBNP concentrations.

Combined clopidogrel and proton pump inhibitor therapy is associated with higher cardiovascular event rates after percutaneous coronary intervention: a report from the BASKET trial.

OBJECTIVE: To investigate whether there is an increased risk of cardiac events with a combined therapy of clopidogrel and proton pump inhibitors (PPIs) after percutaneous coronary intervention (PCI). DESIGN: In the BAsel Stent Kosten Effektivitäts Trial (BASKET), all patients undergoing PCI received 6 months of clopidogrel and were analysed for the use of PPI therapy. Endpoints were major adverse cardiac events (MACE), myocardial infarction (MI), death and target vessel revascularization (TVR) after 36 months. RESULTS: Of 801 patients with available discharge medication data, 109 (14%) received PPIs. Patients who received PPIs were older (66.5 ± 10.5 vs. 63.3 ± 11.3 years, P = 0.006), more likely to be woman (80% vs. 69%, P = 0.009) and have a history of diabetes (29.6% vs. 17.3%, P = 0.002) or gastrointestinal ulcer disease (8.3% vs. 3.3%, P = 0.015) and more often received nonsteroidal anti-inflammatory drugs (7.3% vs. 2.2%, P = 0.003) and corticosteroids (11% vs. 3.6%, P = 0.001) but not aspirin (91.7% vs. 97%, P = 0.008) compared with those who did not receive PPIs. Patients who received PPI therapy had higher rates of MACE (30.3% vs. 20.8%, P = 0.027) and MI (14.7% vs. 7.4%, P = 0.01) but similar rates of death (9.2% vs. 7.4%, P = 0.51) and TVR (20.2% vs. 15.3%, P = 0.2) compared with those who did not. By multivariate analysis, diabetes (hazard ratio 1.83, 95% confidence interval 1.07-3.15) and PPI use (hazard ratio 1.88, 95% confidence interval 1.05-3.37) were the only independent risk factors for MI. CONCLUSION: In a real-world PCI population, the combination of PPIs and clopidogrel was associated with a doubling of MI rates after 3 years. Even after correction for confounding factors, concomitant PPI use remained an independent predictor of outcome emphasizing the clinical importance of this drug-drug interaction.

Primary PCI in STEMI--dilemmas and controversies: multivessel disease in STEMI patients. Complete versus Culprit Vessel revascularization in acute ST--elevation myocardial infarction.

The best strategy regarding percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) in multivessel disease is an unresolved issue. Although current guidelines recommend that PCI in non-culprit arteries should not be attempted unless the patient is hemodynamically unstable, it is unclear whether PCI of the infarct-related artery only or a strategy of complete revascularization, either in a simultaneous or staged multivessel PCI approach, will improve outcome. Based on available data, PCI of the culprit lesion has the advantages of shorter procedure duration, a smaller amount of dye used, and a lower rate of periprocedural myocardial infarctions, while complete revascularization has lower rates of recurrent angina and a better left ventricular ejection fraction. Although data available give controversial results for the right strategy to choose, the only adequately powered randomized controlled trial shows that a strategy of multivessel PCI should be pursued notwithstanding the timing of complete revascularization. However, to avoid the potential risks of simultaneous multivessel PCI, a strategy of staged complete revascularization appears to be the best choice. It should be considered whether current guidelines should be changed to account for these considerations, and other adequately powered randomized controlled trials should be performed to endorse current knowledge.

Time dependence of left ventricular recovery after delayed recanalization of an occluded infarct-related coronary artery: findings of a pilot study.

OBJECTIVES: We sought to test the hypothesis that late recanalization of infarct-related coronary arteries (IRAs) improves long-term left ventricular (LV) function. BACKGROUND: Reperfusion within 24 h of an acute myocardial infarction (MI) has been shown to improve myocardial healing and to reduce infarct expansion. Uncontrolled data suggest that there may be a time window of several weeks for such an effect. METHODS: Sixteen asymptomatic patients 10 +/- 4 days after a first Q wave anterior wall MI with persistent left anterior descending coronary artery occlusion and infarct-zone akinesia were randomized to immediate (2 weeks) or delayed (3 months) angioplasty. Repeat catheterization and cardiac magnetic resonance imaging (MRI) were performed after 3 and 12 months. RESULTS: Angiography 3 months after MI revealed that LV ejection fraction (LVEF) had increased ([mean +/- SD] 54.4 +/- 4.3% vs. 63.9 +/- 7.4%, p < 0.01) as a result of improved regional function (p < 0.01) and LV end-systolic volume had decreased (p < 0.002), whereas LV end-diastolic volume remained unchanged. With delayed angioplasty, LVEF, infarct zone wall motion and LV volumes did not improve. Cardiac MRI at baseline and at 3 and 12 months confirmed these findings and extended them up to 1 year, indicating that delayed angioplasty could no longer improve LV function because of marked LV dilation (p < 0.01). Immediate angioplasty had a high success rate, but restenosis (50%) was accompanied by new severe angina as a clinical indicator of salvaged myocardium, which did not occur after delayed angioplasty. CONCLUSIONS: This pilot study in selected patients supports the hypothesis that myocardial viability persists ("hibernation") for 2 to 3 weeks but not for 3 months after MI, during which time it may be worthwhile to restore blood flow to a large myocardial territory, even in asymptomatic patients, to improve long-term LV function.

Reproducibility of ejection-fraction determinations by equilibrium radionuclide angiography in response to supine bicycle exercise: concise communication.

Sixteen patients with stable, chronic coronary artery disease were studied twice within and average of 15 days to evaluate the reproducibility of ejection fraction (EF) determined by equilibrium radionuclide angiography (EQ) at rest, during supine bicycle exercise (ex), and in the recovery period (rec). Following injection of 20--25 mCi of Tc-99m-tagged human serum albumin, data were analyzed for 2-min periods at rest, during several stages of exercise (submax, max), and during recovery (rec1 = minutes 2 + 3, rec2 = minutes 9 + 10). Each patient reached similar (heart rate) X (blood pressure) products in the two studies: 21280 +/- 5200 compared with 20390 +/- 4140 mmHg/min. Mean EFs for the first and second studies were: at rest (53.0 +/- 10.8)%, 52.5 +/- 10.4)% (r = 0.95; submax ex (51.4 +/- 12.0)%, (52.1 +/- 12.8)%, (r = 0.91); max ex (50.6 +/- 12.6)%, (51.6 +/- 12.9)% (r = 0.97); rec1 (62.7 +/- 11.6)%, (62.4 +/- 12.2)% (r = 0.95); rec2 (55.5 %/- 10.8)%, (57.2 +/- 11.7)% (r = 0.91). In stable patients, the reproducibility of EF determined by EQ is excellent during rest, supine bicycle exercise, and recovery from exercise.

Validity of left-ventricular ejection fractions measured at rest and peak exercise by equilibrium radionuclide angiography using short acquisition times.

To validate ejection fraction (EF) calculations from 5 and 2 minutes of multiple-gated equilibrium radionuclide angiographic data and to establish its utility during alterations in cardiac performance, we studied 38 patients with chest pain suggestive of coronary artery disease. Twenty-four patients underwent contrast ventriculography (CV) as well as first-pass (FP) and equilibrium (EQ) radionuclide angiography at rest, and 14 additional patients had both radionuclide tests performed at rest as well as during peak supine bicycle exercise. The resting 5-min acquisition ejection fractions were compared between each method and the following correlations were generated: r = .92, n = 24 (CV-EQ), r = .92, n = 24 (CV-FP), and r = .95, n = 38 (FP-EQ). The variability of EQ-EF calculations between two independent observers was less than 2%; the mean absolute difference between two sequential 2-min acquisitions and the 5-min recordings was -.1 +/- 1.6%, and the reproducibility of sequential 2-min ejection fractions was excellent (r = .98). EQ and FP ejection fractions at symptom-limited exercise correlated well (r = .96, n = 14). We conclude that equilibrium radionuclide angiography is a valid method to measure EF both at rest as well as during peak exercise even when 2-min acquisition periods are used.

Prevention of supraventricular tachyarrhythmias after open heart operation by low-dose sotalol: a prospective, double-blind, randomized, placebo-controlled study.

BACKGROUND: The aim of this prospective, double-blind, placebo-controlled trial was to assess the preventive effect and safety of low-dose sotalol after heart operation. METHODS: Two hundred fifty-five consecutive patients referred for elective coronary artery bypass grafting (n = 220) or aortic valve operation (n = 35) were randomized to receive either 80 mg of sotalol twice daily (n = 126) or matching placebo (n = 129) for 3 months, with the first dose given 2 hours before operation. RESULTS: There were no significant baseline differences between the groups. Overall, supraventricular tachyarrhythmias occurred in 36% of patients (82% atrial fibrillation). Hospital stay was 11.6 +/- 5 days in patients with supraventricular arrhythmias, versus 9.5 +/- 2.4 days in patients without it (p < 0.0001). Low-dose sotalol reduced the rate of supraventricular arrhythmias from 46% (placebo) to 26% (sotalol; p = 0.0012), or by 43%. On the fourth postoperative day, heart rate was lower in the sotalol group (74 +/- 12 beats/min versus 85 +/- 15 beats/min; p < 0.0001) but the QT interval corrected for the heart rate was not prolonged (sotalol group, 0.44 +/- 0.03 second; placebo group, 0.43 +/- 0.03 second; p = not significant). Study medication had to be discontinued because of side effects in 5.6% of sotalol and 3.9% of placebo patients (p = not significant), with one possible proarrhythmic event occurring in a patient receiving sotalol. CONCLUSIONS: Because more than 90% of supraventricular arrhythmic episodes occurred within 9 days after operation and 70% of all possibly sotalol related side effects occurred after day 9, the findings in this study imply that prophylactic treatment with sotalol may be limited to the first 9 postoperative days.

Long-term outcome of angioplasty for multivessel coronary disease: importance and price of complete revascularization.

BACKGROUND: Complete revascularization of multivessel coronary artery disease (MVD) by coronary artery bypass surgery has been shown to improve outcome, but there is a lack of similar data for patients treated by angioplasty. METHODS: Therefore, a consecutive series of 250 patients with MVD was separated into two groups, those with complete revascularization (n=101) and those with incomplete revascularization (n=149). Six-month 'clinical restenosis' rate assessed by stress myocardial perfusion scintigraphy or symptom-driven angiography and long-term 32 months outcome were compared with an equally sized group of single vessel disease (SVD) patients. RESULTS: MVD patients with complete revascularization had a higher 'clinical restenosis' rate than patients with SVD (35 vs. 22%, P<0.02), although restenosis rate per treated vessel was similar (23%, 18%, P NS). If this higher early restenosis rate were accepted as 'price' for complete MVD angioplasty, long-term event-free survival was no longer different from that of SVD patients (86 vs. 93%, P NS). In contrast, patients with incomplete multivessel angioplasty had a significantly worse long-term outcome (22% events), especially if initially untreated, non-occluded vessels remained untreated (25% events). CONCLUSION: MVD angioplasty with complete revascularization has a long-term event-free survival similar to that of SVD angioplasty but at the price of a higher rate of 6-month restenosis and repeat interventions.

High intensity transcranial Doppler signals (hits) after prosthetic valve implantation.

High intensity transcranial Doppler signals (HITS), assumed to be caused by microemboli, have been reported to occur in many patients with mechanical heart valve prostheses. The aim of our study was to quantify these phenomena and to find possible differences. Furthermore, parameters which might influence the prevalence of HITS were investigated. Monitoring of both middle cerebral artery frequency shift spectra was carried out for 10 minutes in 100 patients having an aortic (n = 64) and (n = 5)/or (n = 31) mitral mechanical heart valve prosthesis. The spectra were off-line screened for HITS by ear. The findings were correlated with the degree of anticoagulation and with the time period since implantation. To examine if platelet aggregates would be the underlying cause, another HITS count was done for 10 minutes prior to and 40 minutes after i.v. injection of 250 mg aspirin (ASA) as well as after four days of 100 mg/day ASA orally in a group of seven patients. Prior to surgery, HITS were present in only one patient. Postoperatively, HITS were detected in 54 of 100 patients. There was no significant difference between left and right sides, no correlation with anticoagulation, and only a borderline correlation with the time interval since implantation. Sixty-six percent of the 50 patients monitored within the first three postoperative weeks had HITS as compared to only 42% in 50 subjects who were examined three months or later after surgery (p < 0.05). With regard to the number of HITS an inverse behaviour was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Silent coronary artery disease in patients with diabetes mellitus.

Coronary artery disease (CAD) represents the leading cause of death in diabetic patients. Silent myocardial ischaemia more often occurs in diabetics than in non-diabetics. It has been well recognised that silent myocardial ischaemia is not different from symptomatic ischaemia with respect to prognosis and adverse events. Asymptomatic high-risk diabetic patients therefore might benefit from routine screening for silent ischaemia and risk stratification; furthermore, silent ischaemia has to be treated accordingly.

Elevated troponin levels in absence of coronary artery disease after supraventricular tachycardia.

Generally speaking elevated troponin levels are consistent with the diagnosis of acute coronary syndrome and haemodynamically relevant coronary artery stenosis. However, they may also point to minor myocardial injury in other circumstances. Four patients with elevated troponin levels after supraventricular tachycardia without evidence of coronary artery disease and very low risk scores for acute coronary syndrome are described and discussed.

Accuracy of biplane analysis of left ventricular ejection fraction based on two consecutive single plane studies.

BACKGROUND AND PURPOSE: Mainly due to the high costs of biplane equipment many cardiac laboratories run single plane angiographic equipment only. Consequently, a biplane ventriculogram may only be done with two consecutive single plane studies. The aim of this investigation was to assess the accuracy of a biplane analysis of two consecutive single plane studies. METHODS: A total of 42 patients (62 +/- 10 years, 76% males), able to tolerate two consecutive ventriculograms without arrhythmia during the first study underwent two consecutive biplane studies (LAO 60, RA0 30), using 40 ml of contrast each. After the first injection, the x-ray tube was moved in a neutral position, and then was replaced in the 30 RAO/60 LAO position. Digital data was analyzed by two separate investigators using commercially available software. RESULTS: Intra-observer variability of left ventricular ejection fraction (LVEF) showed a high degree of agreement (single plane 1 vs. 2: r = 0.98; standard error of regression (Sy.x.): 2.8); the variability was slightly higher with two investigators (single plane: r = 0.92, Sy.x: 5.5 ) and with biplane analysis (biplane 1 vs. 2: r = 0.90, Sy. x: 5.7). End-diastolic volume index (EDVI) increased significantly from the first to the second study (84 +/- 28 ml/m2 vs 87 +/- 30 ml/m2; p = 0.017): Still LVEF of the two consecutive biplane studies showed very good agreement (biplane 1 vs. 2: mean difference (MD), -1.0; standard deviation of the difference (SDD), 5.2%). This agreement was almost as good as the one of LVEF values calculated from two consecutive single plane, but biplane analyzed studies compared to simultaneous biplane studies (MD, -0.5; SDD, 4.3%). CONCLUSION: Despite the significant increase in EDVI after contrast injection, LVEF values determined from two consecutive studies remained virtually unchanged. Biplane analysis of LVEF values based on consecutive single plane studies resulted in similar and reliable values as determined by two consecutive biplane studies.

[Diagnosis of heart failure with radionuclide ventriculography]. / Diagnose der Herzinsuffizienz mittels Radionuklidventrikulographie.

Radionuclide ventriculography is presented as noninvasive scintigraphic method to assess the pump function of the heart. Its role in diagnosis and prognosis of congestive heart failure is described. Advantages and limitations of this technique as compared to echocardiography are discussed, and the importance of left-ventricular ejection fraction in the evaluation of congestive heart failure is critically reviewed.

Benefit of angiographic spontaneous reperfusion in STEMI: does it extend to diabetic patients?

BACKGROUND: Spontaneous reperfusion (SR) in ST elevation myocardial infarction (STEMI) improves clinical outcome, yet its incidence and impact among diabetic patients is unclear. OBJECTIVE: To carry out a systematic analysis of SR in the diabetic cohort of a large primary percutaneous coronary intervention (PCI)-treated population with STEMI. METHODS AND RESULTS: 4944 patients (15.5% diabetic) undergoing primary PCI in the APEX AMI study were evaluated. SR defined as pre-PCI Thrombolysis in Myocardial Infarction (TIMI) 3 flow occurred in 11.5% of patients; it was more common in non-diabetic (11.9%) than in diabetic patients (9.2%) (p = 0.028). Patients with SR versus no SR had improved post-PCI TIMI 3 flow: in non-diabetic patients (99.8% vs 90.3%, p<0.001) and in diabetic patients (98.6% vs 84.9%, p<0.001). Non-diabetic patients with SR showed a significant improvement in 90-day death/shock/congestive heart failure (CHF) compared with those without SR: 4.4% versus 8.9% (p = 0.001), respectively. The composite outcome in diabetic patients with versus without SR was 10.0% versus 14.9% (p = 0.270), respectively. When outcomes were examined according to tertiles of baseline blood glucose, both non-diabetic and diabetic patients with normoglycaemia showed higher SR rates (15.5%, 10.3%, 7.3% for non-diabetic patients, p<0.001; 17.4%, 7.2%, 9.1% for diabetic patients, p = 0.132), greater ST resolution (55.4%, 52.6%, 49.7% for non-diabetic patients, p = 0.030; 50%, 46.4%, 39.1% for diabetic patients, p = 0.179), and improved 90-day death/shock/CHF (5.2%, 8.3%, 14% for non-diabetic patients p<0.001; 8.7%, 4.2%, 15.8% for diabetic patients, p = 0.006). CONCLUSIONS: These data indicate that SR is less common in diabetic patients with STEMI. Diabetic patients without SR have worse post-PCI epicardial patency, which contributes to adverse outcomes. Diabetic patients with normal baseline blood glucose and SR have enhanced epicardial flow after PCI and improved prognosis.

[Pain killers--killing the pain or the patient?]. / Nichtsteroidale Antirheumatika und Coxibe--die sanften Herzensbrecher?

Over the last years, the coxibes were widely used as potent and well tolerated pain killers. This was in part due to the better gastrointestinal tolerability of the coxibes. On the other hand the higher cox-2 selectivity is consistent with a higher cardio-vascular event rate in patients with coxibe therapy which has been demonstrated by several studies. Side effects are probably caused by the interaction of the following factors: impact on thrombocytes, coagulation, blood vessel physiology, and blood pressure. Of note, the reported cardio-vascular adverse event rates in trials evaluating coxibes and older non-steroidal anti-inflammatory drugs was very low. Furthermore, there were no difference in fatal event rates. This underscores the need to carefully deliberate about the beneficial and potentially harmful use of these drugs. In daily practice it therefore might be suitable to still use these drugs to alleviate pain in selected patients.

Stunning and left ventricular function--how long is the ventricle knocked out? Left ventricular function correlated with ischemic burden and recovery time after stress.

PURPOSE: Little is known about the relation between severity of ischemia and duration of myocardial stunning. The aim of this study was therefore to characterize the impact of ischemia on myocardial stunning and on its duration. METHODS: 310 patients (pts) who underwent myocardial perfusion SPECT (MPS) were evaluated. MPS acquired with a rest Thallium/stress Technetium-99m sestamibi protocol were scored with respect to % myocardium ischemic. Left ventricular post-stress ejection fraction (psEF) was evaluated by the widely used QGS algorithm. Resting LVEF (rEF) was assessed by invasive ventriculography. Patient groups were then compared with respect to different extents of ischemia and different time intervals between stress and imaging (< or = 60 min and > 60 min after stress). RESULTS: 21% of pts had a normal MPS, 8% had evidence of scar, 37% had evidence of ischemia, and 34% had evidence of scar plus ischemia. Pts with normal MPS had a significantly higher psEF than pts with ischemia, 61+/-8% and 56+/-8%, respectively (p=0.006), whereas rEF was not different. Overall, pts with < or = 10% myocardium ischemic had significantly higher psEF than pts with > 10% myocardium ischemic, 53+/-11% and 49+/-9%, respectively (p=0.006), whereas rEF was not different. In pts with evidence of ischemia who underwent imaging < or = 60 min after stress testing, pts with < or = 10% myocardium ischemic had higher psEF than pts with > 10% myocardium ischemic, 60+/-7% and 53+/-8%, respectively (p=0.037). In contrast, pts with evidence of ischemia who underwent imaging > 60 min after stress testing had similar psEF irrespective of extent of ischemia (53%+/-8 in pts with < or = 10% ischemia and 54%+/-8 in pts with > 10% myocardium ischemic, p=0.12). CONCLUSIONS: Ischemia had a significant impact on psEF in patients who underwent imaging less than 1 h after stress. More than one hour after stress testing stunning seems to be less relevant in the interpretation of psEF.

["HAART-attack" in young female HIV-patient]. / "HAART-Attack" bei junger HIV-Patientin.

Since the implementation of highly active antiretroviral therapy (HAART) there is a dramatic decline in morbidity and mortality due to reduction of opportunistic infections in HIV-infected patients resulting in improved prognosis. Unfortunately, patients receiving HAART are at risk for metabolic complications, which may induce the development of coronary artery and cerebrovascular disease, particularly in young patients and in the presence of additional cardiovascular risk factors. A 30-years old female HIV-infected patient who developed an acute myocardial infarction is described.

Coronary artery disease and outcome in acute congestive heart failure.

OBJECTIVES: To quantify the prognostic impact of coronary artery disease (CAD) on patients with acute heart failure (HF). DESIGN: Prospective cohort study of 217 consecutive patients presenting with acute HF to the emergency department. Treatment, hospitalisation, the use of revascularisation procedures, and survival were observed during follow up of up to three years. RESULTS: CAD was present in 153 patients (71%). Patients with and without CAD were similar with respect to age and sex. Although adequate HF treatment was initiated more rapidly among patients with CAD, their initial outcomes including hospitalisation rate, time to discharge, and total treatment cost were significantly worse. Moreover, despite higher use of angiotensin converting enzyme inhibitors and beta blockers during follow up, patients with CAD had a significantly lower survival rate. Cumulative survival at 720 days was 48.7% of patients with CAD as compared with 76.4% of patients without CAD (p = 0.0004). In Cox regression analysis the presence of CAD increased the risk of death by more than 250% (hazard ratio 2.57, 95% confidence interval 1.50 to 4.39, p = 0.001). This strong association persisted after multivariate adjustments. The use of coronary angiography and coronary revascularisation procedures was low, both at initial presentation and during follow up. CONCLUSION: CAD is a strong and independent predictor of mortality among patients with acute HF. Whether, for example, less restrictive use of revascularisation procedures in this elderly HF population can improve the outcome for patients with CAD warrants further study.