Beatrice A. Marzluf

Cardiac Magnetic Resonance Postcontrast T1 Time Is Associated With Outcome in Patients With Heart Failure and Preserved Ejection Fraction

Background—The underlying pathophysiology of heart failure with preserved ejection fraction (HFPEF) is incompletely understood, but myocardial extracellular matrix accumulation is thought to play a major role. Our aims were to estimate myocardial extracellular matrix using cardiac magnetic resonance T1 mapping and to assess the relationship between pathobiology/pathophysiology and prognosis. Methods and Results—Patients with suspected HFPEF (n=100) were enrolled in this prospective, observational study. Confirmatory diagnostic tests, cardiac magnetic resonance imaging including T1 mapping, and invasive hemodynamic assessments were performed at baseline. Sixty-one patients with confirmed HFPEF entered a longitudinal outcome-monitoring phase (mean, 22.9±5.0 months), during which 16 had a cardiac event. Cardiac magnetic resonance T1 time (hazard ratio, 0.99; 95% confidence interval, 0.98–0.99; P=0.046), left atrial area (hazard ratio, 1.08; 95% confidence interval, 1.03–1.13; P<0.01), and pulmonary vascular resistance (hazard ratio, 1.01; 95% confidence interval, 1.00–1.01; P=0.03) were significantly associated with cardiac events. Patients with T1 times below the median (<388.3 ms) were at greater risk of cardiac events than the rest of the group (P<0.01). Extracellular matrix of left ventricular biopsies (n=9), quantified by TissueFAXS technology correlated with T1 time (R=0.98; P<0.01). T1 time also correlated with right ventricular–pulmonary arterial coupling (pulmonary vascular resistance: R=−0.36; P<0.01; right ventricular ejection fraction: R=0.28; P=0.01). Conclusions—In the present preliminary study, cardiac magnetic resonance postcontrast T1 time is associated with prognosis in HFPEF, suggesting postcontrast T1 as possible biomarker for HFPEF.

T1 Mapping by CMR Imaging: From Histological Validation to Clinical Implication

OBJECTIVES The purpose of this study was to prospectively investigate the diagnostic and prognostic impact of cardiac magnetic resonance (CMR) T1 mapping and validate it against left ventricular biopsies. BACKGROUND Extracellular volume (ECV) expansion is a key feature of heart failure. CMR T1 mapping has been developed as a noninvasive technique to estimate ECV; however, the diagnostic and prognostic impacts of this technique have not been well established. METHODS A total of 473 consecutive patients referred for CMR (49.5% female, age 57.8 ± 17.1 years) without hypertrophic cardiomyopathy, cardiac amyloidosis, or Anderson-Fabry disease were studied. T1 mapping with the modified Look-Locker inversion recovery (MOLLI) sequence was used for ECV calculation (CMR-ECV). For methodological validation, 36 patients also underwent left ventricular biopsy, and ECV was quantified by TissueFAXS analysis (TissueFAXS-ECV). To assess the prognostic value of CMR-ECV, its association with hospitalization for cardiovascular reasons or cardiac death was tested in a multivariable Cox regression model. RESULTS TissueFAXS-ECV was 26.3 ± 7.2% and was significantly correlated with CMR-ECV (r = 0.493, p = 0.002). Patients were followed up for 13.3 ± 9.0 months and divided into CMR-ECV tertiles for Kaplan-Meier analysis (tertiles were ≤ 25.7%, 25.8% to 28.5%, and ≥ 28.6%). Significantly higher event rates were observed in patients with higher CMR-ECV (log-rank p = 0.013). By multivariable Cox regression analysis, CMR-ECV was independently associated with outcome among imaging variables (p = 0.004) but not after adjustment for clinical parameters. CONCLUSIONS CMR T1 mapping allows accurate noninvasive quantification of ECV and is independently associated with event-free survival among imaging parameters. Its prognostic value on top of established clinical risk factors warrants further investigation in long-term studies.

The right heart in heart failure with preserved ejection fraction: insights from cardiac magnetic resonance imaging and invasive haemodynamics.

Recent data indicate that right ventricular systolic dysfunction (RVSD) by cardiac magnetic resonance imaging (CMR) is a strong predictor of outcome in heart failure. However, the prognostic significance of RVSD by CMR in heart failure with preserved ejection fraction (HFpEF) is unknown.

Right Ventricular Dysfunction, But Not Tricuspid Regurgitation, Is Associated With Outcome Late After Left Heart Valve Procedure

BACKGROUND Significant tricuspid regurgitation (TR) late after left heart valve procedure is frequent and associated with increased morbidity. Surgical correction carries a significant mortality risk, whereas the impact of TR on survival in these patients is unclear. OBJECTIVES This study sought to assess the impact of significant TR late after left heart valve procedure. METHODS A total of 539 consecutive patients with previous left heart valve procedure (time interval from valve procedure to enrollment 50 ± 30 months) were prospectively followed for 53 ± 15 months. RESULTS Significant TR (defined as moderate or greater severity by echocardiography) was present in 91 (17%) patients (65% female). Patients with TR presented with more symptoms (New York Heart Association functional class ≥II 55% vs. 31%), lower glomerular filtration rates (61 ± 19 ml/min vs. 68 ± 18 ml/min), and a higher likelihood of atrial fibrillation (41% vs. 20%), all statistically significant. Right ventricular (RV) systolic function was worse in patients with significant TR (RV fractional area change 43 ± 11% vs. 47 ± 9%, p < 0.001). A total of 117 (22%) patients died during follow-up. By Kaplan-Meier analysis, overall survival was significantly worse in patients with significant TR (log-rank p < 0.001). However, by multivariable Cox analysis, only RV fractional area change, age, left atrial size, diabetes, and previous coronary artery bypass graft procedure were significantly associated with mortality, but not tricuspid regurgitation. CONCLUSIONS RV dysfunction, but not significant TR, is independently associated with survival late after left heart valve procedure.

Strength training increases maximum working capacity in patients with COPD--randomized clinical trial comparing three training modalities.

BACKGROUND AND OBJECTIVE Skeletal muscle dysfunction contributes to exercise limitation in patients with chronic obstructive pulmonary disease (COPD). Strength training increases muscle strength and muscle mass, but there is an ongoing debate on the additional effect concerning the exercise capacity. The purpose of this study was to compare the effects of three different exercise modalities in patients with COPD including endurance training (ET), progressive strength training (ST) and the combination of strength training and endurance training (CT). DESIGN A prospective randomized trial. METHODS Thirty-six patients with COPD were randomly allocated either to ET, ST, or CT. Muscle strength, cardiopulmonary exercise testing, lung function testing and quality of life were assessed before and after a 12-week training period. RESULTS Exercise capacity (Wmax) increased significantly in all three training groups with increase of peak oxygen uptake (VO2peak) in all three groups, reaching statistical significance in the ET group and the CT group. Muscle strength (leg press, bench press, bench pull) improved in all three training groups, with a higher improvement in the ST (+39.3%, +20.9%, +20.3%) and the CT group (+43.3%, +18.1%, +21.6%) compared to the ET group (+20.4%, +6.4%, +12.1%). CONCLUSIONS Progressive strength training alone increases not only muscle strength and quality of life, but also exercise capacity in patients with COPD, which may have implications in prescription of training modality. CLINICALTRIALS.GOV IDENTIFIER: NCT01091623.

Abnormal pulmonary arterial pressure limits exercise capacity in patients with COPD

ZusammenfassungZIELE: Das Vorliegen einer pulmonalen Hypertension ist häufig bei Patienten mit chronisch obstruktiver Lungenerkrankung (COPD) anzutreffen. Der mittlere pulmonalarterielle Druck (mPAP) ist in Ruhe oft nur gering erhöht, zeigt aber einen pathologischen Anstieg unter Belastung. Das Ziel dieser Studie ist es, die Leistungsfähigkeit und den pulmonalen Gasaustausch bei COPD Patienten mit und ohne pulmonalarterieller Hypertension zu untersuchen. PATIENTEN UND METHODEN: Bei 42 Patienten mit COPD Grad II-IV (28 Männer, 14 Frauen) wurden eine Bodyplethysmographie, eine symptomlimitierte Fahrradergospirometrie sowie eine Rechtsherzkatheteruntersuchung durchgeführt. RESULTATE: 32 von 42 Patienten (76%) zeigten einen erhöhten mPAP in Ruhe (PH mPAP = 26,8 ± 5,9 mmHg), bei 10 Patienten war der mPAP in Ruhe im Normbereich (NPH, mPAP = 16,8 ± 2 mmHg). Es gab keinen signifikanten Unterschied hinsichtlich der lungenfunktionellen Parameter in beiden Gruppen. Die maximale Sauerstoffaufnahme (VO2max) war signifikant niedriger in der PH Gruppe (785 ± 244 ml/min) im Vergleich zur NPH Gruppe (1052 ± 207 ml/min, p = 0,004). Es zeigte sich in der PH Gruppe eine erhöhte Totraumventilation mit signifikant erhöhtem Atemäquivalent für CO2 (VECO2 47,3 ± 10 vs 38,6 ± 3,5, p = 0,025) und signifikant höherem arterio-endtidalen CO2 Partialdruck [p(a-ET)CO2]. Der pulmonalarterielle Widerstand (PVR) in Ruhe zeigte eine negative Korrelation hinsichtlich der VO2max, VE/VCO2 und dem arterio-endtidalen CO2 Partialdruck [p(a-ET)CO2]. ZUSAMMENFASSUNG: Patienten mit COPD und erhöhter pulmonalarterieller Druckwerte in Ruhe zeigen eine Verschlechterung des pulmonalen Gasaustausches unter Belastung, eine Beeinträchtigung der maximalen Sauerstoffaufnahme und somit eine limitierte Leistungsfähigkeit.SummaryOBJECTIVE: Pulmonary hypertension (PH) is common in patients with chronic obstructive pulmonary disease (COPD). Mean pulmonary artery pressure (mPAP) is often only slightly elevated at rest but is increased by exercise. The purpose of this study was to determine whether abnormal pulmonary artery pressure impairs exercise capacity in patients with COPD. PATIENTS AND METHODS: 42 patients with moderate-to-very-severe COPD (28 men, 14 women) underwent symptom-limited incremental cardiopulmonary exercise testing and also right-heart catheterization at rest. Abnormal pulmonary artery pressure was defined as mPAP > 20 mmHg at rest. RESULTS: Resting mPAP was elevated in 32 patients (PH, mPAP = 26.8 ± 5.9 mmHg) and normal in 10 non-hypertensive (NPH) patients (NPH, mPAP = 16.8 ± 2 mmHg). There were no significant differences in lung function between the PH and NPH groups. Maximum oxygen uptake during exercise (VO2max) was significantly lower in PH (785 ± 244 ml/min) than in NPH (1052 ± 207 ml/min, P = 0.004). Dead-space ventilation (Vd/Vt) was greater in PH (P = 0.05) with higher VE/VCO2 (ratio of minute ventilation to carbon dioxide output = 47.3 ± 10 vs 38.6 ± 3.5, P = 0.025) and significantly higher arterial-end-tidal pCO2 difference [p(a-ET)CO2]. Pulmonary vascular resistance measured at rest correlated significantly with VO2max, VE/VCO2 and p(a-ET)CO2. CONCLUSIONS: In patients with COPD, abnormal pulmonary artery pressure impairs gas exchange, decreases maximum oxygen uptake during exercise and impairs exercise capacity.

Interstitial Fibrosis, Functional Status, and Outcomes in Heart Failure With Preserved Ejection FractionCLINICAL PERSPECTIVE: Insights From a Prospective Cardiac Magnetic Resonance Imaging Study

Background—Myocardial extracellular volume (ECV) accumulation is one of the key pathophysiologic features of heart failure with preserved ejection fraction (HFpEF). Our aims were to (1) measure ECV by cardiac magnetic resonance T1 mapping using the modified Look-Locker inversion recovery (MOLLI) sequence, (2) validate MOLLI-ECV against histology, and (3) investigate the relationship between MOLLI-ECV and prognosis in HFpEF. Methods and Results—One-hundred seventeen consecutive HFpEF patients underwent cardiac magnetic resonance imaging, coronary angiography, and invasive hemodynamic assessments at baseline. Eighteen patients also underwent left ventricular biopsy for histological analysis (Histo-ECV). To assess the prognostic impact of MOLLI-ECV, its association with hospitalization for heart failure/cardiac death was tested by multivariable Cox regression analysis. Histo-ECV was 30.1±4.6% and was significantly correlated with MOLLI-ECV (R=0.494, P=0.037). Patients were followed for 24.0 months (6.0–32.0 months), during which 34 had a cardiac event. By Kaplan–Meier analysis, patients with MOLLI-ECV ≥ the median (28.9%) had shorter event-free survival (log-rank, P=0.028). MOLLI-ECV significantly correlated with N-terminal prohormone of brain natriuretic peptide (P<0.001), 6-minute walk distance (P=0.004), New York Heart Association functional class (P=0.009), right atrial pressure (P=0.037), and stroke volume (P=0.043). By multivariable Cox regression analysis, MOLLI-ECV was associated with outcome among imaging variables (P=0.038) but not after adjustment for clinical and invasive hemodynamic parameters. Conclusions—We demonstrate that MOLLI-ECV in HFpEF accurately reflects histological ECV, correlates with markers of disease severity, and is associated with outcome among cardiac magnetic resonance parameters but not after adjustment for important clinical and invasive hemodynamic parameters. Nevertheless, MOLLI-ECV has the potential of becoming an important biomarker in HFpEF.

Vasoactive intestinal peptide (VIP) receptor expression in monocyte-derived macrophages from COPD patients.

Vasoactive intestinal peptide (VIP) is one of the most abundant molecules found in the respiratory tract. Due to its anti-inflammatory and bronchodilatatory properties, it has been proposed as a novel treatment for chronic obstructive pulmonary disease (COPD). The actions of VIP are mediated via three different G-protein-coupled receptors (VPAC1, VPAC2 and PAC1) which are expressed in the respiratory tract and on immunocompetent cells including macrophages. Alveolar macrophages (AM) are key players in the pathogenesis of COPD and contribute to the severity and progression of the disease. While VPAC1 has been reported to be elevated in subepithelial cells in smokers with chronic bronchitis, little is known about VPAC expression of AM in COPD patients. AM from COPD patients show a strong VPAC1 expression which exceeds VPAC2. A similar receptor expression pattern was also observed in lipopolysaccharide (LPS)-activated monocyte-derived macrophages (MDM) from healthy volunteers and COPD patients. VIP has been shown to down-regulate interleukin 8 (IL-8) secretion significantly in MDM after LPS stimulation. The response to VIP was similar in MDM from COPD patients and healthy volunteers. Our results indicate that VPAC1 up-regulation in macrophages is a common mechanism in response to acute and chronic pro-inflammatory stimuli. Although VPAC1 up-regulation is dominant, both receptor subtypes are necessary for optimal anti-inflammatory signaling. The high VPAC1 expression in AM may reflect the chronic pro-inflammatory environment found in the lung of COPD patients. Treatment with VIP may help to decrease the chronic inflammation in the lung of COPD patients.

Influence of drug adherence and medical care on heart failure outcome in the primary care setting in Austria

Guideline‐recommended therapy has been proven beneficial in heart failure (HF), but general implementation remains poor. The aim of this study was to evaluate the adherence to drug therapy, quality of primary non‐drug medical care (NDMC) and its impact on HF outcome.

Prognostic Impact of Tricuspid Regurgitation in Patients Undergoing Aortic Valve Surgery for Aortic Stenosis

Background The prognostic significance of tricuspid regurgitation (TR) and right ventricular (RV) function in patients undergoing aortic valve replacement (AVR) for severe aortic stenosis (AS) is unknown. The aim of the present study was to evaluate the impact of TR and RV systolic dysfunction on early and late mortality in this setting. Methods This was a prospective single-center observational study. 465 consecutive patients who were referred to AVR for severe AS were investigated. Significant TR was defined as TR≥moderate by transthoracic echocardiography. Results At baseline, significant TR was present in 26 (5.6%) patients. Patients with TR presented with a higher EuroSCORE I (p = 0.001), a higher incidence of previous cardiac surgery (p<0.001), pulmonary hypertension (p = 0.003), more dilated RVs (p = 0.001), and more frequent RV dysfunction (p = 0.001). Patients were followed for an average of 5.2 (±2.8 SD) years. By multivariable Cox regression analysis TR (p = 0.014), RV dysfunction (p = 0.046), age (p = 0.001) and concomitant coronary artery bypass graft surgery (CABG, p = 0.003) were independently associated with overall mortality. By Kaplan-Meier analysis, survival rates were significantly worse in patients with significant than with non-significant TR (log rank p = 0.001). Conclusions TR, RV dysfunction, age, and concomitant CABG are associated with outcome in patients undergoing AVR for severe AS. This finding underlines the importance of a thorough echocardiographic evaluation with particular consideration of the right heart in these patients.