Riociguat in pulmonary hypertension and heart failure with preserved ejection fraction: the haemoDYNAMIC trial.

AIMS: The presence of pulmonary hypertension (PH) severely aggravates the clinical course of heart failure with preserved ejection fraction (HFpEF). To date, neither established heart failure therapies nor pulmonary vasodilators proved beneficial. This study investigated the efficacy of chronic treatment with the oral soluble guanylate cyclase stimulator riociguat in patients with PH-HFpEF. METHODS AND RESULTS: The phase IIb, randomized, double-blind, placebo-controlled, parallel-group, multicentre DYNAMIC trial assessed riociguat in PH-HFpEF. Patients were recruited at five hospitals across Austria and Germany. Key eligibility criteria were mean pulmonary artery pressure ≥25 mmHg, pulmonary arterial wedge pressure >15 mmHg, and left ventricular ejection fraction ≥50%. Patients were randomized to oral treatment with riociguat or placebo (1:1). Patients started at 0.5 mg three times daily (TID) and were up-titrated to 1.5 mg TID. The primary efficacy endpoint was change from baseline to week 26 in cardiac output (CO) at rest, measured by right heart catheterization. Primary efficacy analyses were performed on the full analysis set. Fifty-eight patients received riociguat and 56 patients placebo. After 26 weeks, CO increased by 0.37 ± 1.263 L/min in the riociguat group and decreased by -0.11 ± 0.921 L/min in the placebo group (least-squares mean difference: 0.54 L/min, 95% confidence interval 0.112, 0.971; P = 0.0142). Five patients dropped out due to riociguat-related adverse events but no riociguat-related serious adverse event or death occurred. CONCLUSION: The vasodilator riociguat improved haemodynamics in PH-HFpEF. Riociguat was safe in most patients but led to more dropouts as compared to placebo and did not change clinical symptoms within the study period.

Prevalence of early repolarization syndrome and long-term clinical outcome in patients with the diagnosis of idiopathic ventricular fibrillation.

Idiopathic ventricular fibrillation (IVF) is diagnosed in up to 14% of sudden cardiac death (SCD) survivors. Early repolarization syndrome (ERS) in patients with ventricular tachyarrhythmia is characterized by an elevated J-point in inferior and/or antero-lateral leads. Our objectives were to determine the prevalence of ERS in IVF patients, and to evaluate potential differences in clinical outcome. Out of 3,552 implantable cardioverter defibrillator (ICD) carriers, 758 SCD survivors were retrospectively identified from the databases of the Medical Universities of Vienna and Innsbruck within the last three decades. Early repolarization pattern (ERP) was classified either as "notching" or "slurring". Endpoints were defined as appropriate ICD therapies for ventricular tachyarrhythmia, either anti-tachycardia pacing or shock, and all-cause mortality. After exclusion of recognized reasons for SCD, 50 patients were assigned to the diagnosis of IVF (6.6%). An ERP was identified in 10 patients, most of them with notching (n = 8). After a mean follow-up of 11.2 ± 6.7 years (539.3 patient years), appropriate ICD therapies were found in 50% of ERS and 43% of IVF patients without ERP (p = 0.732). In ERS patients, all ICD therapies were found in patients with notching pattern. Similarly, incidence of inappropriate ICD therapies, and all-cause mortality was comparable (30% vs. 23%, p = 0.707; 10% vs. 5%, p = 0.496, respectively). In 758 SCD survivors, we found a low prevalence of IVF and ERS. Similar event rates were reported concerning all-cause mortality and ICD therapies for ventricular tachyarrhythmia after long-term follow-up in this cohort.

Incidence of late-acquired stent malapposition of drug eluting stents with second generation permanent and biodegradable polymer coatings-A prospective, randomized comparison using optical coherence tomography.

OBJECTIVES AND BACKGROUND: Polymer coatings of drug-eluting stents (DES) may induce allergic reactions and inflammation, resulting in late-acquired stent malapposition (LASM) with the risk of stent thrombosis. This study evaluated, if biodegradable polymer (BP) reduces the incidence of LASM compared to permanent polymer (PP) after treatment with newer generation DES. METHODS AND RESULTS: Fifty patients with 59 lesions were randomized (2:1) to elective treatment with second generation PP-DES (n = 32, 39 stents), either Everolimus-eluting or Zotarolimus-eluting stents, or with BP-DES (Biolimus-eluting stents [BES]; n = 18, 20 stents) and underwent optical coherence tomography directly after implantation and after 1 year. After implantation acute stent malappositions (ASM) were documented in 30 stents (51%) distributed to 22 stents treated with PP-DES (56%) and 8 with BP-DES (40%; n.s.). After 1 year, late stent malappositions (LSM) were detected in 14 stents (24 %); ASM persisted (APSM) in 9 stents after one year (7 PP-DES-18%, 2 BES-10%), whereas ASM resolved in 21 stents. In addition, LASM was documented in nine stents including five stents without and four stents with additional APSM. All LASM were located in PP-DES (n = 9; 23%), none in BP-DES (P = 0.022). Compared to the reference lumen area, in-stent lumen area of stents without LASM was smaller due to neointimal hyperplasia (P = 0.021), whereas in-stent lumen area at maximum LASM of stents with LASM was larger due to positive remodeling (P = 0.002). CONCLUSIONS: In conclusion the use of BP-DES reduced the occurrence of LASM due to positive remodeling compared to second generation PP-DES.

Long-term physical activity leads to a significant increase in serum sRAGE levels: a sign of decreased AGE-mediated inflammation due to physical activity?

There is growing evidence that low levels of the circulating soluble receptor of advanced glycation end products (sRAGE) are a valuable predictor of cardiovascular disease (CVD). The aim of this prospective study was to investigate the influence of long-term physical activity on serum sRAGE levels. 109 subjects were recruited, and 98 completed the study. Participants were asked to perform exercise within the calculated training pulse for 8 months. The performance gain was measured/quantified by bicycle stress tests at the beginning and end of the observation period. sRAGE was measured at baseline and after 2/6/8 months by ELISA. Backwards, multiple linear regression analysis was performed to investigate the association of co-variables age, sex, BMI, and performance at baseline, HbA1c, and lipoprotein a with baseline sRAGE levels. We identified BMI and lipoprotein a as significant predictors for baseline sRAGE levels. Compared to subjects with a performance gain ≤ 4.9% subjects with a gain > 5% showed a significant increase in sRAGE levels up to 22%. sRAGE serum levels correlate negatively with lipoprotein a levels and BMI and long-term physical activity leads to a significant increase in serum sRAGE levels (9-22%), whereby the sRAGE increase is most pronounced in subjects with initially low-performance levels, suggesting that in particular, these subject profit the most from increased physical activity. The sport-mediated increase of sRAGE might be a sign of decreased AGE-mediated inflammation and highlight the protective effect of sports on CVD and other disease which are at least partly mediated by an increased inflammation status.Clinical trials registration NCT02097199.

Diameter of the Pulmonary Artery in Relation to the Ascending Aorta: Association with Cardiovascular Outcome.

Purpose To investigate whether the pulmonary artery (PA)-to-ascending aorta (Ao) ratio is associated with outcome in unselected patients referred for cardiac magnetic resonance (MR) imaging. Materials and Methods This study prospectively enrolled 650 consecutive patients (47.2% women; mean age, 56.1 years ± 17.7 [standard deviation]). Diameters of PA and Ao were measured in axial black blood images. On the basis of previous results, a PA-to-Ao ratio of 1.0 or greater was chosen as the cutoff for further analysis. Univariable and multivariable Cox regression models were used to investigate the primary end point, which was defined as a composite of cardiovascular hospitalization and death. Results A PA-to-Ao ratio of 1.0 or greater was present in 131 (20.2%) patients. Patients with a PA-to-Ao ratio of 1.0 or greater were predominantly women (P = .010); more frequently presented with atrial fibrillation (P < .001), diabetes (P < .001), and impaired renal function (P < .001); and had higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (P < .001), larger left (P = .023) and right ventricles (RV; P = .002), and worse RV function (P < .001). Patients were followed for 17.8 months ± 12.9, during which 110 patients (16.9%) reached the primary end point. By Kaplan-Meier analysis, event-free survival was significantly worse in patients with a PA-to-Ao ratio of 1.0 or greater (log-rank test, P < .001). A PA-to-Ao ratio of 1.0 or greater was independently associated with outcome by multivariable Cox regression analysis, in addition to age, NT-proBNP serum levels, and RV size. Conclusion A PA-to-Ao ratio of 1.0 or greater identified patients at risk, most likely because of elevated PA pressures. On the basis of these results, the PA-to-Ao ratio should routinely be reported at cardiac MR imaging. © RSNA, 2017 Online supplemental material is available for this article.

Mechanical properties of the everolimus-eluting bioresorbable vascular scaffold compared to the metallic everolimus-eluting stent.

BACKGROUND: Everolimus-eluting bioresorbable vascular scaffolds (BVS) represent an innovative treatment option for coronary artery disease. Clinical and angiographic results seem promising, however, data on its immediate procedural performance are still scarce. The aim of our study was to assess the mechanical properties of BVS by Optical Coherence Tomography (OCT) in clinical routine. METHODS: Post-implantation OCT images of 40 BVS were retrospectively compared to those of 40 metallic everolimus-eluting stents (EES). Post-procedural device related morphological features were assessed. This included incidences of gross underexpansion and the stent eccentricity index (SEI, minimum/maximum diameter) as a measure for focal radial strength. RESULTS: Patients receiving BVS were younger than those with EES (54.0 ± 11.2 years versus 61.7 ± 11.4 years, p = 0.012), the remaining baseline, vessel and lesion characteristics were comparable between groups. Lesion pre-dilatation was more frequently performed and inflation time was longer in the BVS than in the EES group (n = 34 versus n = 23, p = 0.006 and 44.2 ± 12.8 versus 25.6 ± 8.4 seconds, p < 0.001, respectively). There were no significant differences in maximal inflation pressures and post-dilatation frequencies with non-compliant balloons between groups. Whereas gross device underexpansion was not significantly different, SEI was significantly lower in the BVS group (n = 12 (30 %) versus n = 14 (35 %), p = 0.812 and 0.69 ± 0.08 versus 0.76 ± 0.09, p < 0.001, respectively). There was no difference in major adverse cardiac event-rate at six months. CONCLUSION: Our data show that focal radial expansion was significantly reduced in BVS compared to EES in a clinical routine setting using no routine post-dilatation protocol. Whether these findings have impact on scaffold mid-term results as well as on clinical outcome has to be investigated in larger, randomized trials.

Comparison of magnetic wire navigation with the conventional wire technique for percutaneous coronary intervention of chronic total occlusions: a randomised, controlled study.

Wire crossing of a chronic total coronary occlusion (CTO) is time consuming and limited by the amount of contrast agent and time of radiation exposure. Magnetic wire navigation (MWN) might accelerate wire crossing by maintaining a coaxial vessel orientation. This study compares MWN with the conventional approach for recanalization of CTOs. Forty symptomatic patients with CTO were randomised to MWN (n = 20) or conventional approach (n = 20) for antegrade crossing of the occlusion. In the intention-to-treat analysis, MWN showed a shorter crossing time (412 versus 1131 s; p = 0.001), and, consequently, lower usage of contrast agent (primary endpoint 42 versus 116 ml; p = 0.01), and lower radiation exposure (dose-area product: 29 versus 80 Gy*cm(2); p = 0.002) during wire crossing compared to the conventional approach. Accordingly, in the per-protocol analysis, the wire-crossing rate was, in trend, higher using the conventional approach (17 of 31) compared to MWN (9 of 28; p = 0.08). The use of MWN for revascularisation of CTOs is feasible and reduces crossing time, use of contrast agent, and radiation exposure. However, due to a broader selection of wires, the conventional approach enables wire crossing in cases failed by MWN and seems to be the more successful choice.

Amyloid Burden Correlates with Electrocardiographic Findings in Patients with Cardiac Amyloidosis-Insights from Histology and Cardiac Magnetic Resonance Imaging.

Cardiac amyloidosis (CA) is associated with several distinct electrocardiographic (ECG) changes. However, the impact of amyloid depositions on ECG parameters is not well investigated. We therefore aimed to assess the correlation of amyloid burden with ECG and test the prognostic power of ECG findings on outcomes in patients with CA. Consecutive CA patients underwent ECG assessment and cardiac magnetic resonance imaging (CMR), including the quantification of extracellular volume (ECV) with T1 mapping. Moreover, seven patients underwent additional amyloid quantification using immunohistochemistry staining of endomyocardial biopsies. A total of 105 CA patients (wild-type transthyretin: 74.3%, variant transthyretin: 8.6%, light chain: 17.1%) were analyzed for this study. We detected correlations of total QRS voltage with histologically quantified amyloid burden (r = -0.780, p = 0.039) and ECV (r = -0.266, p = 0.006). In patients above the ECV median (43.9%), PR intervals were significantly longer (p = 0.016) and left anterior fascicular blocks were more prevalent (p = 0.025). In our survival analysis, neither Kaplan-Meier curves (p = 0.996) nor Cox regression analysis detected associations of QRS voltage with adverse patient outcomes (hazard ratio: 0.995, p = 0.265). The present study demonstrated that an increased amyloid burden is associated with lower voltages in CA patients. However, baseline ECG findings, including QRS voltage, were not associated with adverse outcomes.

Austrian consensus statement on the diagnosis and management of hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease that is characterized by left ventricular hypertrophy unexplained by secondary causes. Based on international epidemiological data, around 20,000-40,000 patients are expected to be affected in Austria. Due to the wide variety of clinical and morphological manifestations the diagnosis can be difficult and the disease therefore often goes unrecognized. HCM is associated with a substantial reduction in quality of life and can lead to sudden cardiac death, especially in younger patients. Early and correct diagnosis, including genetic testing, is essential for comprehensive counselling of patients and their families and for effective treatment. The latter is especially true as an effective treatment of outflow tract obstruction has recently become available in the form of a first in class cardiac myosin ATPase inhibitor, as a noninvasive alternative to established septal reduction therapies. The aim of this Austrian consensus statement is to summarize the recommendations of international guidelines with respect to the genetic background, pathophysiology, diagnostics and management in the context of the Austrian healthcare system and resources, and to present them in easy to understand algorithms.

Impact of tafamidis on myocardial strain in transthyretin amyloid cardiomyopathy.

AIMS: The impact of tafamidis on myocardial strain in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) have been barely investigated. We aimed to determine tafamidis-induced changes using serial speckle tracking echocardiography and to identify imaging parameters for specific therapy monitoring. METHODS AND RESULTS: ATTR-CM patients underwent serial TTE with two-dimensional (2 D) speckle tracking imaging. Patients receiving tafamidis free acid 61 mg (n = 62) or tafamidis meglumine 20 mg (n = 21) once daily (QD) showed stable measurements at follow-up (61 mg: 8.5 months, 20 mg: 7.0 months) in LV global longitudinal strain (GLS) (61 mg: -11.75% vs. -11.58%, p = 0.534; 20 mg: -10.61% vs. -10.12%, p = 0.309), right ventricular (RV) GLS (61 mg: -14.18% vs. -13.72%, p = 0.377; 20 mg: -14.53% vs. -13.99%, p = 0.452) and left atrial (LA) reservoir strain (LASr; 61 mg: 8.80% vs. 9.42%, p = 0.283; 20 mg: 8.23% vs. 8.67%, p = 0.589), whereas treatment-naïve ATTR-CM patients (n = 54) had clear signs of disease progression at the end of the observation period (10.5 months; LV-GLS: -11.71% vs. -10.59%, p = 0.001; RV-GLS: -14.36% vs. -12.99%, p = 0.038; LASr: 10.67% vs. 8.41%, p = 0.005). Between-group comparison at follow-up revealed beneficial effects of tafamidis free acid 61 mg on LASr (p = 0.003) and the LV (LV-GLS: p = 0.030, interventricular septum (IVS): p = 0.006), resulting in clinical benefits (six-minute walk distance (6-MWD): p = 0.006, NT-proBNP: p= <0.001), while patients treated with tafamidis meglumine 20 mg QD showed positive effects on LASr (p = 0.039), but no differences with respect to the LV (LV-GLS: p = 0.274, IVS: p = 0.068) and clinical status (6-MWD: p = 0.124, NT-proBNP: p = 0.053) compared to the natural course. CONCLUSIONS: Treatment with tafamidis free acid 61 mg in ATTR-CM patients delays the deterioration of LA and LV longitudinal function, resulting in significant clinical benefits compared with natural history. Serial TTE with 2 D speckle tracking imaging may be appropriate for disease-specific therapy monitoring.