Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder associated with “cardiovascular stress”, i.e. cardiovascular risk factors, cardiovascular diseases, and an increased risk of ...heart failure, stroke, and death. Experimental and clinical studies have characterized potential underlying mechanisms including biventricular dysfunction, atherosclerosis, and arrhythmia. Assessment of these cardiovascular features of OSA requires a spectrum of clinical tools including ECG, echocardiography, exercise testing, and angiography. In contrast to many cardiovascular diseases, the role of blood biomarkers to characterize cardiovascular function and cardiovascular risk in OSA is poorly defined. In the present review we summarize the available data on biomarkers potentially providing information on cardiovascular features in OSA patients without overt cardiovascular disease. The vast majority of studies on biomarkers of cardiovascular stress in OSA evaluated B-type natriuretic peptide (BNP)/N-terminal-B-type natriuretic peptide (NT-proBNP), and cardiac troponins (cTn). Although some studies found significant associations between these cardiac biomarkers and the presence and severity of OSA, data remain conflicting. Also, the detailed pathophysiological mechanisms underlying the link between OSA and hemodynamic cardiac stress (BNP/NT-proBNP) and cardiomyocyte damage (cTn) are poorly understood. Major research efforts are required to establish the clinical role of cardiovascular biomarkers in patients with OSA.
•Obstructive sleep apnea (OSA) is associated with increased cardiovascular risk.•There are no established biomarkers for diagnosis or risk stratification in OSA.•Some studies showed an association between OSA severity and natriuretic peptides and cardiac troponins.•Overall data on natriuretic peptides and cardiac troponins in OSA are conflicting.
A patient with hypertrophic obstructive cardiomyopathy (HOCM) was admitted with acute heart failure. Echocardiography revealed significantly worsened left ventricular outflow tract obstruction and ...pulmonary hypertension. Cardiac magnetic resonance imaging showed biventricular dysfunction and, as an unexpected finding, a large embolus in the right pulmonary artery. The patient gradually improved with medical therapy including oral anticoagulation. In HOCM patients, pulmonary embolism may trigger heart failure due to impaired left ventricular filling with consecutive outflow tract obstruction provocation.
Un patient atteint de cardiomyopathie obstructive hypertrophique (COH) a été admis pour insuffisance cardiaque aiguë. L'échocardiographie a révélé une aggravation significative de l'obstruction de la voie d'éjection du ventricule gauche et une hypertension pulmonaire. L'imagerie par résonance magnétique cardiaque a révélé une dysfonction biventriculaire et, fait inattendu, un embole important dans l'artère pulmonaire droite. L'état du patient s'est progressivement amélioré grâce à un traitement médical comprenant une anticoagulation orale. Chez les patients atteints de COH, l'embolie pulmonaire peut déclencher une insuffisance cardiaque due à une altération du remplissage du ventricule gauche avec induction consécutive d'une obstruction de la voie d'éjection.
The relationship between longitudinal clinical congestion pattern and heart failure outcome is uncertain. This study was designed to assess the prevalence of congestion over time and to investigate ...its impact on outcome in chronic heart failure.
A total of 588 patients with chronic heart failure older than 60 years of age with New York Heart Association (NYHA) functional class ≥II from the TIME-CHF study were included. The endpoints for this study were survival and hospitalization-free heart failure survival. Orthopnea, NYHA ≥III, paroxysmal nocturnal dyspnea, hepatomegaly, peripheral pitting edema, jugular venous distension, and rales were repeatedly investigated and related to outcomes. These congestion-related signs and symptoms were used to design a 7-item Clinical Congestion Index.
Sixty-one percent of patients had a Clinical Congestion Index ≥3 at baseline, which decreased to 18% at month 18. During the median interquartile range follow-up of 27.2 14.3-39.8 months, 17%, 27%, and 47% of patients with baseline Clinical Congestion Index of 0, 1-2, and ≥3 at inclusion, respectively, died (P <.001). Clinical Congestion Index was identified as an independent predictor of mortality at all visits (P <.05) except month 6 and reduced hospitalization-free heart failure survival (P <.05). Successful decongestion was related to better outcome as compared to persistent congestion or partial decongestion (log-rank P <0.001).
The extent of congestion as assessed by means of clinical signs and symptoms decreased over time with intensified treatment, but it remained present or relapsed in a substantial number of patients with heart failure and was associated with poor outcome. This highlights the importance of appropriate decongestion in chronic heart failure.
Background
In aortic stenosis (AS), estimated glomerular filtration rate (eGFR) is an important prognostic marker but its haemodynamic determinants are unknown. We investigated the correlation ...between eGFR and invasive haemodynamics and long‐term mortality in AS patients undergoing aortic valve replacement (AVR).
Methods
We studied 503 patients median (interquartile range) age 76 (69–81) years with AS indexed aortic valve area .42 (.33–.49) cm2/m2 undergoing cardiac catheterization prior to surgical (72%) or transcatheter (28%) AVR. Serum creatinine was measured on the day before cardiac catheterization for eGFR calculation (CKD‐EPI formula).
Results
The median eGFR was 67 (53–82) mL/min/1.73 m2. There were statistically significant correlations between eGFR and mean right atrial pressure (r = −.13; p = .004), mean pulmonary artery pressure (mPAP; r = −.25; p < .001), mean pulmonary artery wedge pressure (r = −.19; p < .001), pulmonary vascular resistance (r = −.21; p < .001), stroke volume index (r = .16; p < .001), extent of coronary artery disease, and mean transvalvular gradient but not indexed aortic valve area. In multivariate linear regression, higher age, lower haemoglobin, lower mean transvalvular gradient (i.e. lower flow), lower diastolic blood pressure, and higher mPAP were independent predictors of lower eGFR. After a median post‐AVR follow‐up of 1348 (948–1885) days mortality was more than two‐fold higher in patients in the first eGFR quartile compared to those in the other three quartiles hazard ratio 2.18 (95% confidence interval 1.21–3.94); p = .01.
Conclusion
In patients with AS, low eGFR is a marker of an unfavourable haemodynamic constellation as well as important co‐morbidities. This may in part explain the association between low eGFR and increased post‐AVR mortality.
In 503 patients with severe aortic stenosis undergoing cardiac catheterization prior to valve replacement, there were statistically significant correlations between eGFR and mRAP (r = −.13), mean pulmonary artery pressure (mPAP; r = −.25), mean pulmonary artery wedge pressure (r = −.19), and pulmonary vascular resistance (r = −.21). Higher age, lower haemoglobin, lower mean transvalvular gradient, lower diastolic blood pressure, and higher mPAP were independent predictors of lower eGFR. Long‐term mortality was more than two‐fold higher in patients in the first compared to the other three eGFR quartiles.
In patients with severe aortic stenosis (AS), atrial fibrillation (AF) is associated with increased long-term mortality after aortic valve replacement (AVR), which may be due to unfavorable ...hemodynamics in AF. We aimed to analyze the hemodynamic profile of patients with severe AS and AF versus sinus rhythm (SR).
We performed cardiac catheterization in 486 patients (age 74 ± 10 years, 58% males) with severe AS indexed aortic valve area 0.41 ± 0.13 cm2, left ventricular ejection fraction 58 ± 12%: 50 patients had AF, and 436 patients had SR. All patients underwent surgical (n = 350) or transcatheter (n = 136) AVR.
Despite similar indexed aortic valve area (0.41 ± 0.11 vs. 0.41 ± 0.12 cm2/m2; p = 0.45) patients with AF had lower left ventricular ejection fraction, larger left atrial size, lower tricuspid annular plane systolic excursion, higher mean pulmonary artery pressure (34 ± 13 vs. 24 ± 9 mmHg), mean pulmonary artery wedge pressure (mPAWP; 22 ± 8 vs. 15 ± 7 mmHg), and pulmonary vascular resistance (2.8 ± 1.9 vs. 2.0 ± 1.3 Wood units) and lower stroke volume index (26 ± 9 vs. 37 ± 10 ml/m2) than patients with SR (p < 0.05 for all). Patients with AF and SR had a different mPAWP-left ventricular end-diastolic pressure (LVEDP) relationship with higher mPAWP in AF and higher LVEDP in SR. After a median follow-up of 49 (interquartile range, 35–64) months post-AVR patients with AF (p = 0.05) and patients with a larger difference between mPAWP and LVEDP (p = 0.005) had higher mortality.
Patients with severe AS and concomitant AF have a distinct and significantly worse hemodynamic profile compared to patients with SR associated with worse clinical outcome.
•Patients with AS and AF have worse hemodynamics compared to those with SR.•In AS patients, those with AF and SR have a different mPAWP to LVEDP relationship.•Patients with AS and AF have higher mortality after valve replacement versus SR.
Elevated cardiac troponin I (cTnI) is frequently observed in patients with severe sepsis and septic shock. However, the mechanisms underlying cTnI release in these patients are still unknown. To date ...no data regarding coagulation disturbances as a possible mechanism for cTnI release during sepsis are available.
Consecutive patients with systemic inflammatory response syndrome (SIRS), sepsis or septic shock without evidence of an acute coronary syndrome were analyzed. Coagulation parameters (clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), alpha-angle) were assessed in native whole blood samples, and using specific activators to evaluate the extrinsic and intrinsic as well as the fibrin component of the coagulation pathway with the use of rotational thrombelastometry (ROTEM). Thirty-eight patients were included and 22 (58%) were cTnI-positive. Baseline characteristics between TnI-positive and -negative patients were similar. The CT, CFT, MCF and the alpha-angle were similar between the groups with trends towards shorter CT in the extrinsic and fibrin activation.
We found no differences in coagulation parameters analyzed with rotational thrombelastometry between cTnI-positive and -negative patients with SIRS, severe sepsis, and septic shock. These findings suggest that pathophysiological mechanisms other than thrombus-associated myocardial damage might play a major role, including reversible myocardial membrane leakage and/or cytokine mediated apoptosis in these patients.
Aims
Renal failure is a major challenge in treating heart failure (HF) patients. HF medication may deteriorate renal function, but the impact thereof on outcome is unknown. We investigated the ...effects of HF medication on worsening renal function (WRF) and the relationship to outcome.
Methods and results
This post‐hoc analysis of TIME‐CHF (NT‐proBNP‐guided vs. symptom‐guided management in chronic HF) included patients with LVEF ≤45% and ≥1 follow‐up visit (n = 462). WRF III was defined as a rise in serum creatinine ≥0.5 mg/dL (i.e. 44.2 µmol/L) at any time during the first 6 months. Four classes of medication were considered: loop diuretics, beta‐blockers, renin–angiotensin system (RAS)‐blockers, and spironolactone. Functional principal component analysis of daily doses was used to comprehend medication over time. All‐cause mortality after 18 months was the primary outcome. Interactions between WRF, medication, and outcome were tested. Patients with WRF III received on average higher loop diuretic doses (P = 0.0002) and more spironolactone (P = 0.02), whereas beta‐blockers (P = 0.69) did not differ and lower doses of RAS‐blockers were given (P = 0.09). There were significant interactions between WRF III, medicationn and outcome. Thus, WRF III was associated with poor prognosis if high loop diuretic doses were given (P = 0.001), but not with low doses (P = 0.29). The opposite was found for spironolactone (poor prognosis in the case of WRF III with no spironolactone, P <0.0001; but not with spironolactone, P = 0.31). Beta‐blockers were protective in all patients (P <0.001), but most in those with WRF III (P <0.05 for interaction). RAS‐blockade was associated with improved outcome (P = 0.006), irrespective of WRF III.
Conclusion
Based on this analysis, it may be hypothesized that high doses of loop diuretics might have detrimental effects, particularly in combination with significant WRF, whereas spironolactone and beta‐blockers might be protective in patients with WRF.
The role of the electrocardiogram for risk stratification in patients with severe aortic stenosis is not established. We assessed the hemodynamic correlates and the prognostic value of the corrected ...QT interval (QTc) in patients with severe aortic stenosis undergoing aortic valve replacement.
The QT interval was measured in a 12-lead electrocardiogram in 485 patients (age 74 ± 10 years, 57% male) with severe aortic stenosis (indexed aortic valve area 0.41 ± 0.13 cm2/m2, left ventricular ejection fraction 58 ± 12%) the day prior to cardiac catheterization. Prolonged QTc was defined as QTc >450 ms in men and QTc >470 ms in women. The outcome parameter was all-cause mortality.
Patients with prolonged QTc (n = 100; 77 men, 23 women) had similar indexed aortic valve area but larger left ventricular and left atrial size, lower left ventricular ejection fraction, more severe mitral regurgitation, lower cardiac index, and higher mean pulmonary artery pressure, mean pulmonary artery wedge pressure, and pulmonary vascular resistance, as compared with patients with normal QTc (n = 385). After a median follow-up of 3.7 years (interquartile range, 2.6-5.2) after surgical (n = 349) or transcatheter (n = 136) aortic valve replacement, patients with prolonged QTc had higher mortality than those with normal QTc (hazard ratio 2.81 95% confidence interval, 1.51-5.20; P < .001). Prolonged QTc was an independent predictor of death along with more severe mitral regurgitation and higher pulmonary vascular resistance.
In patients with severe aortic stenosis, prolonged QTc is a marker of an advanced disease stage associated with an adverse hemodynamic profile and increased long-term mortality after aortic valve replacement.
Contrast nephropathy (CN) accounts for significant morbidity and mortality. Patients with pre-existing renal insufficiency, especially those with diabetic nephropathy, are at particular risk. ...Medullary hypoxia due to decreased renal blood flow and direct cytotoxicity contribute to the pathogenesis. Contrast nephropathy is usually defined as an increase in serum creatinine concentration >0.5 mg/dl or 25% above the baseline level within 48 h. Intravenous hydration (saline 0.45%, if tolerated 0.9% at a rate of 1 ml/kg/h) 12 h before and after contrast exposure and the use of low or iso-osmolality contrast agents are advisable. The benefit of low-dose dopamine as well as the selective dopamine-1 receptor agonist fenoldopam is unproven. Studies on the effectiveness of the adenosine antagonist theophylline have led to conflicting results. Because theophylline has a narrow therapeutic range and may be associated with adverse effects, it is not a prophylactic agent of first choice. The administration of N-acetylcysteine (NAC) has been evaluated in several trials with inconsistent results. Newer data suggest a benefit of high-dose NAC (1,200 mg twice daily) for patients receiving high doses (>140 ml) of contrast agent, or those with advanced renal insufficiency (creatinine >2.5 mg/dl). Whereas prophylactic hemodialysis does not prevent CN, a recent study demonstrated a marked benefit of prophylactic hemofiltration.
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