Stephan Blazek

Extracellular Volume Fraction for Characterization of Patients With Heart Failure and Preserved Ejection Fraction.

BACKGROUND Optimal patient characterization in heart failure with preserved ejection fraction (HFpEF) is essential to tailor successful treatment strategies. Cardiac magnetic resonance (CMR)-derived T1 mapping can noninvasively quantify diffuse myocardial fibrosis as extracellular volume fraction (ECV). OBJECTIVES This study aimed to elucidate the diagnostic performance of T1 mapping in HFpEF by examining the relationship between ECV and invasively measured parameters of diastolic function. It also investigated the potential of ECV to differentiate among pathomechanisms in HFpEF. METHODS We performed T1 mapping in 24 patients with HFpEF and 12 patients without heart failure symptoms. Pressure-volume loops were obtained with a conductance catheter during basal conditions and handgrip exercise. Transient pre-load reduction was used to extrapolate the diastolic stiffness constant. RESULTS Patients with HFpEF showed higher ECV (p < 0.01), elevated load-independent passive left ventricular (LV) stiffness constant (beta) (p < 0.001), and a longer time constant of active LV relaxation (p = 0.02). ECV correlated highly with beta (r = 0.75; p < 0.001). Within the HFpEF cohort, patients with ECV greater than the median showed a higher beta (p = 0.05), whereas ECV below the median identified patients with prolonged active LV relaxation (p = 0.01) and a marked hypertensive reaction to exercise due to pathologic arterial elastance (p = 0.04). On multiple linear regression analyses, ECV independently predicted intrinsic LV stiffness (β = 0.75; p < 0.01). CONCLUSIONS Diffuse myocardial fibrosis, assessed by CMR-derived T1 mapping, independently predicts invasively measured LV stiffness in HFpEF. Additionally, ECV helps to noninvasively distinguish the role of passive stiffness and hypertensive exercise response with impaired active relaxation. (Left Ventricular Stiffness vs. Fibrosis Quantification by T1 Mapping in Heart Failure With Preserved Ejection Fraction [STIFFMAP]; NCT02459626).

Comparison of bare-metal stenting with minimally invasive bypass surgery for stenosis of the left anterior descending coronary artery: 10-year follow-up of a randomized trial.

OBJECTIVES The aim of this prospective, randomized trial was to assess the 10-year long-term safety and effectiveness of percutaneous coronary intervention (PCI) and minimally invasive direct coronary artery bypass surgery (MIDCAB) for the treatment of proximal left anterior descending (LAD) lesions. BACKGROUND Long-term follow-up data comparing PCI and MIDCAB surgery for isolated proximal LAD lesions are sparse. METHODS Patients with significant isolated proximal LAD stenoses were randomized either to PCI with bare-metal stents (n = 110) or MIDCAB (n = 110). At 10 years, data were obtained with respect to the primary endpoint (death, myocardial infarction, target vessel revascularization). Angina was assessed by the Canadian Cardiovascular Society classification. RESULTS Follow-up was conducted for 212 patients at a median time of 10.3 years. There were no significant differences in the binary primary composite endpoint (47% vs. 36%; p = 0.12) and hard endpoints (death and infarction) between PCI and MIDCAB. However, a higher target vessel revascularization rate in the PCI group (34% vs. 11%; p < 0.01) was observed. Clinical symptoms improved significantly from baseline and were similar between both treatment groups. CONCLUSIONS At 10-year follow-up, PCI and MIDCAB in isolated proximal LAD lesions yielded similar long-term outcomes regarding the primary composite clinical endpoint. Target vessel revascularization was more frequent in the PCI group.

Frequency and Significance of Myocardial Bridging and Recurrent Segment of the Left Anterior Descending Coronary Artery in Patients With Takotsubo Cardiomyopathy

Despite intensive research efforts, the causative mechanisms of takotsubo cardiomyopathy (TC) are still unknown. Recently, morphologic characteristics of the left anterior descending coronary artery (LAD) have been proposed as a potential pathophysiological substrate. Hence, the aim of the present study was to evaluate the prevalence of myocardial bridging and LAD recurrent segments in a large cohort of patients with TC. A total of 161 patients with TC were matched for age and gender with 161 controls without coronary artery or valvular heart disease. Myocardial bridging was diagnosed according to indirect signs in coronary angiography. Furthermore, the LAD was evaluated regarding parts of the vessel outreaching the left ventricular apex (LAD recurrent segment). The prevalence of myocardial bridging was similar in the TC and control groups (11.8% vs 6.8%, p = 0.18). Any part of the LAD outreaching the left ventricular apex was observed in 55.6% of patients with TC compared with 35.4% in the control population (p <0.001). Moreover, the LAD supplied ≥ 25% of the inferior myocardial wall in 21 patients with TC (13.1%), whereas patients in the control group did not show this pattern of coronary circulation at all (p <0.001). Patients with TC with typical apical ballooning compared with those with atypical ballooning patterns demonstrated a higher prevalence of myocardial bridging (p = 0.04) but not LAD recurrent segments (p = 0.28). In conclusion, the prevalence of myocardial bridging in patients with TC is low and comparable with that in a matched control group. In contrast, LAD recurrent segments are significantly more frequent in patients with TC.

Growth differentiation factor-15 in Takotsubo cardiomyopathy: Diagnostic and prognostic value

BACKGROUND Growth differentiation factor-15 (GDF-15), a stress responsive cytokine, has emerged as a marker of adverse outcome in various cardiovascular diseases. Since GDF-15 has not been evaluated in patients with Takotsubo cardiomyopathy (TTC), the present study sought to investigate the diagnostic and prognostic value in this patient cohort. METHODS A total of 22 patients presenting with TTC were matched for age and gender with 22 ST-segment elevation myocardial infarction (STEMI) patients. GDF-15 concentrations were measured at admission and 1 day thereafter. The primary clinical endpoint of the TTC cohort was the composite of death, cardiogenic shock, or new congestive heart failure within 6 months. RESULTS TTC patients showed significantly higher GDF-15 values on admission compared to patients presenting with STEMI (median 3047 ng/l [interquartile range 2256-7572] versus median 1527 ng/l [interquartile range 1152-2677]; p=0.002). TTC patients with a biventricular ballooning pattern and patients experiencing major adverse cardiac events during the first 6 months after acute presentation showed significantly higher GDF-15 concentrations on admission (p=0.008 and p=0.005, respectively). Biventricular ballooning was identified as a predictor for elevated GDF-15 values on admission (p=0.03). High GDF-15 levels on admission were the only significant predictor for the combined clinical endpoint in multivariable regression analysis (p=0.02). CONCLUSION TTC patients showed markedly high, but transient elevation of GDF-15 levels. Biventricular ballooning was associated with particularly high GDF-15 concentrations. Elevated GDF-15 values on admission were a strong predictor of adverse clinical outcome.

Assessment of acute changes in ventricular volumes, function, and strain after interventional edge-to-edge repair of mitral regurgitation using cardiac magnetic resonance imaging.

AIMS Whereas haemodynamic and echocardiographic studies suggest benefits for left ventricular (LV) function and cardiac output following reduction in LV preload by interventional edge-to-edge repair for mitral regurgitation (MR), there is limited data on volumetric and functional LV and right ventricular (RV) changes using cardiac magnetic resonance (CMR) imaging. METHODS AND RESULTS Patients with moderate to severe MR and high surgical risk underwent MitraClip-implantation and CMR imaging before and within 7 days after the procedure. In addition to volumetric and flow studies, myocardial feature tracking (FT) technology for quantification of myocardial strain was applied. Twenty patients (age: 76 ± 8 years) with functional (n = 15) or degenerative MR (n = 5) with a mean logistic Euroscore I of 33 ± 16 underwent both successful MitraClip implantation and CMR imaging. MR fraction (36 ± 10 vs. 19 ± 12%; P < 0.001) and LV end-diastolic volume (115 ± 36 vs. 105 ± 41 mL/m2; P = 0.002) decreased significantly, whereas LV ejection fraction (42 ± 15 vs. 41 ± 16%, P = 0.8) and cardiac index (1.7 ± 0.5 vs. 1.8 ± 0.4 L/min/m2, P = 0.4) remained unchanged. MitraClip implantation resulted in a significant impairment of circumferential (-12.8 ± 4.8 vs. -8.2 ± 3.3; P = 0.002) and radial strain (15.4 ± 7.7 vs. 9.6 ± 5.3; P = 0.02) on basal short-axis view. On RV level, there were no significant changes in end-diastolic volume (83 ± 19 vs. 84 ± 18 mL/m2, P = 0.8), ejection fraction (42 ± 9 vs. 43 ± 11%, P = 0.8), or tricuspid regurgitation fraction (24 ± 17 vs. 25 ± 19%, P = 0.7). MitraClip implantation led to a significant improvement in New York Heart Association functional class (patients in functional class III-IV pre 100% vs. post 45%; P < 0.001). CONCLUSION In severely compromised patients, marked reduction in MR by MitraClip implantation might not result in immediate improved cardiac output and effective biventricular forward flow.

Incidence, characteristics and functional implications of cerebral embolic lesions after the MitraClip procedure

AIMS This study aimed to assess the incidence and impact of cerebral embolic events after the MitraClip procedure. METHODS AND RESULTS Twenty-seven high-risk patients (logistic EuroSCORE I 25±15%) underwent the MitraClip procedure and cerebral diffusion-weighted magnetic resonance imaging (MRI) in median two days before and three days after the procedure. On the same day, neurocognitive function was assessed using the Montreal Cognitive Assessment (MoCA) questionnaire and thorough clinical examination. Comparison of pre- and post-interventional MRI showed that 23 of 27 patients (85.7%) had newly acquired microembolic lesions with in median three (interquartile range 1-9) new lesions per patient. Of these, three patients (11.1%) had lesions with diameter >5 mm. Patients with >3 new cerebral embolic lesions (n=13, 48%) had a lower post-interventional MoCA score in comparison to patients with ≤3 embolic lesions (23.6±3.6 vs. 20.3±4.5; p=0.046) in univariate analysis. Multivariate stepwise regression analysis identified device time as an independent predictor of the number of post-procedural new lesions (p=0.003) and, for reduced post-interventional MoCA score, a low MoCA score at baseline (p<0.001). CONCLUSIONS The MitraClip procedure results in new ischaemic cerebral lesions in the vast majority of patients. Preliminary data suggest that these lesions are clinically without significant impact on global cognitive function. ClinicalTrials.gov: NCT01288976.

Influence of Left Atrial Function on Exercise Capacity and Left Ventricular Function in Patients With Heart Failure and Preserved Ejection FractionCLINICAL PERSPECTIVE

Background— Although left atrial (LA) dysfunction is common in heart failure with preserved ejection fraction (HFpEF), its functional implications beyond the reflection of left ventricular (LV) pathology are not well understood. The aim of this study was to further characterize LA function in HFpEF patients. Methods and Results— We performed cardiac magnetic resonance myocardial feature tracking in 22 patients with HFpEF and 12 patients without HFpEF. LA reservoir strain, LA conduit strain, and LA booster pump strain were quantified. Peak oxygen uptake (VO2max) was determined. Invasive pressure–volume loops were obtained to evaluate LV diastolic properties. LV early filling was determined from LV volume–time curves as derived from cardiac magnetic resonance. LA reservoir and conduit strain were significantly lower in HFpEF (LA reservoir strain, 22±7% versus 29±6%, P=0.04; LA conduit strain, −9±5% versus −15±4%, P<0.01). Patients with HFpEF showed lower oxygen uptake (17±6 versus 29±8 mL/(kg min); P<0.01). Strain measurement for LA conduit function was strongly associated with VO2max (r=0.80; P<0.01). On multivariable regression analysis, LA conduit strain emerged as strongest predictor for VO2max even after inclusion of LV stiffness and relaxation time (&bgr;=0.80; P<0.01). LA conduit strain correlated with the volume of early ventricular filling (r=0.67; P<0.01), but not LV stiffness constant &bgr; (−0.34; P=0.051) or relaxation constant &tgr; (r=−0.33; P=0.06). Conclusions— Cardiac magnetic resonance myocardial feature tracking–derived conduit strain is significantly impaired in HFpEF and associated with exercise intolerance. Impaired conduit function is associated with impaired early ventricular filling, as potential mechanism leading to impaired oxygen uptake. Our results propose that impaired LA conduit function represents a distinct feature of HFpEF, independent of LV stiffness and relaxation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT02459626.

Plasma and Cardiac Galectin-3 in Patients With Heart Failure Reflects Both Inflammation and FibrosisCLINICAL PERSPECTIVE: Implications for Its Use as a Biomarker

Background— Galectin (Gal)-3 is a &bgr;-galactoside-binding lectin and currently intensely studied as a biomarker in heart failure. Gal-3 also exerts proinflammatory effects, at least in extracardiac tissues. Objective of this study was to characterize the relationship of plasma and myocardial Gal-3 levels with cardiac fibrosis and inflammation in patients with nonischemic dilated cardiomyopathy and inflammatory cardiomyopathy (iCMP). Methods and Results— Endomyocardial biopsies and blood samples were obtained from patients with newly diagnosed cardiomyopathy and clinical suspicion of myocarditis. According to histopathologic findings, patients were classified as having dilated cardiomyopathy (n=40) or iCMP (n=75). Cardiac fibrosis was assessed histologically on endomyocardial biopsy sections. In patients with iCMP, myocardial Gal-3 expression significantly correlated with inflammatory cell count on endomyocardial biopsy (r=0.56; P<0.05). In contrast, an inverse association was observed between myocardial Gal-3 expression and cardiac fibrosis in patients with iCMP (r=−0.59; P<0.05). In patients with dilated cardiomyopathy, myocardial Gal-3 expression correlated with cardiac fibrosis on left ventricular biopsy (P=0.63; P<0.01). Of note, in both groups, plasma Gal-3 levels did not correlate with myocardial Gal-3 levels or left ventricular fibrosis, whereas a positive correlation between plasma Gal-3 levels and inflammatory cell count on endomyocardial biopsy was observed in patients with iCMP. Conclusions— The present study suggests that myocardial Gal-3 can be considered as a possible marker for both cardiac inflammation and fibrosis, depending on the pathogenesis of heart failure. However, circulating concentrations of Gal-3 do not seem to reflect endomyocardial Gal-3 levels or cardiac fibrosis.

Pulse Wave Velocity Predicts Response to Renal Denervation in Isolated Systolic Hypertension

Background Renal sympathetic denervation seems to be less effective as a treatment for hypertension in patients with isolated systolic hypertension, a condition associated with elevated central arterial stiffness. Because isolated systolic hypertension can also be caused by wave reflection or increased cardiac output, a more differentiated approach might improve patient preselection for renal sympathetic denervation. We sought to evaluate the additional predictive value of invasive pulse wave velocity for response to renal sympathetic denervation in patients with combined versus isolated systolic hypertension. Methods and Results Patients scheduled for renal sympathetic denervation underwent additional invasive measurement of pulse wave velocity and pulse pressure before denervation. Blood pressure was assessed via ambulatory measurement at baseline and after 3 months. In total 109 patients (40 patients with isolated systolic hypertension) were included in our analysis. After 3 months, blood pressure reduction was more pronounced among patients with combined hypertension compared with patients with isolated systolic hypertension (systolic 24‐hour average 9.3±10.5 versus 5.0±11.5 mm Hg, P=0.046). However, when stratifying patients with isolated systolic hypertension by invasive pulse wave velocity, patients in the lowest tertile of pulse wave velocity had comparable blood pressure reduction (12.1±12.6 mm Hg, P=0.006) despite lower baseline blood pressure than patients with combined hypertension (systolic 24‐hour average 154.8±12.5 mm Hg in combined hypertension versus 141.2±8.1, 148.4±10.9, and 150.5±12.7 mm Hg, respectively, by tertiles of pulse wave velocity, P=0.002). Conclusions Extended assessment of arterial stiffness can help improve patient preselection for renal sympathetic denervation and identify a subgroup of isolated systolic hypertension patients who benefit from sympathetic modulation.

Ultrasound-based renal sympathetic denervation for the treatment of therapy-resistant hypertension: a single-center experience.

Introduction: The effectiveness of renal sympathetic denervation (RDN) as a treatment for therapy-resistant hypertension has been doubted as the Simplicity-HTN-3 trial was unable to show any treatment benefit over sham procedure. This might partly be explained by a high procedural variability in treatment with radiofrequency-based catheters. Recently, newer systems for RDN, like ultrasound-based devices, have been introduced into practice. To date however, data on their effectiveness for the treatment of resistant hypertension are scarce. We sought to evaluate the safety and effectiveness of an ultrasound-based, balloon-irrigated RDN catheter in a larger single-center cohort. Methods: Patients with therapy-resistant hypertension [average blood pressure (BP) >135 mmHg SBP or >90 mmHg DBP in ambulatory BP measurement despite at least three antihypertensive drugs, including at least one diuretic] underwent ultrasound-based RDN. Treatment effect was assessed by comparing BP values at baseline and 3 months after the procedure. Patients underwent renal artery duplex sonography or MRI before and after RDN to exclude renal artery stenosis. Results: Fifty consecutive patients underwent ultrasound-based RDN, of which 25 had undergone an unsuccessful radiofrequency RDN before. Mean SBP change at 3 months was −9.7 ± 12.6/−10.6 ± 13.7/−8.2 ± 15.2 mmHg (ambulatory 24-h mean/daytime/night, P < 0.001 for all) and DBP changed by −5.1 ± 7.4/−5.8 ± 7.8/−3.9 ± 10.3 mmHg (P ⩽ 0.001/<0.001/0.01). No new renal artery stenosis could be detected after RDN. Conclusion: Ultrasound-based RDN seems to be well tolerated and effective for the treatment of patients with therapy-resistant hypertension.