The role of Matrix Metalloproteinase-2 and Galectin-3 as predictive biomarkers for all-cause mortality in patients undergoing transfemoral transcatheter aortic valve implantation.

BACKGROUND: Currently available risk scores fail to accurately predict morbidity and mortality in patients with severe symptomatic aortic stenosis who undergo transcatheter aortic valve implantation (TAVI). In this context, biomarkers like matrix metalloproteinase-2 (MMP-2) and Galectin-3 (Gal-3) may provide additional prognostic information. METHODS: Patients with severe aortic stenosis undergoing consecutive, elective, transfemoral TAVI were included. Baseline demographic data, functional status, echocardiographic findings, clinical outcomes and biomarker levels were collected and analysed. RESULTS: The study cohort consisted of 89 patients (age 80.4 ± 5.1 years, EuroScore II 7.1 ± 5.8%). During a median follow-up period of 526 d, 28 patients (31.4%) died. Among those who died, median baseline MMP-2 (alive: 221.6 [170.4; 263] pg/mL vs. deceased: 272.1 [225; 308.8] pg/mL, p < 0.001) and Gal-3 levels (alive: 19.1 [13.5; 24.6] pg/mL vs. deceased: 25 [17.6; 29.5] pg/mL, p = 0.006) were higher than in survivors. In ROC analysis, MMP-2 reached an acceptable level of discrimination to predict mortality (AUC 0.733, 95% CI [0.62; 0.83], p < 0.001), but the predictive value of Gal-3 was poor (AUC 0.677, 95% CI [0.56; 0.79], p = 0.002). Kaplan-Meier and Cox regression analyses showed that patients with MMP-2 and Gal-3 concentrations above the median at baseline had significantly impaired long-term survival (p = 0.004 and p = 0.02, respectively). CONCLUSIONS: In patients with severe aortic stenosis undergoing transfemoral TAVI, MMP-2 and to a lesser extent Gal-3, seem to have additive value in optimizing risk prediction and streamlining decision-making.

Association of central blood pressure with an exaggerated blood pressure response to exercise among elite athletes.

PURPOSE: The systolic blood pressure/workload (SBP/MET) slope was recently reported to be a reliable parameter to identify an exaggerated blood pressure response (eBPR) in the normal population and in athletes. However, it is unclear whether an eBPR correlates with central blood pressure (CBP) and vascular function in elite athletes. METHODS: We examined 618 healthy male elite athletes (age 25.8 ± 5.1 years) of mixed sports with a standardized maximum exercise test. CBP and vascular function were measured non-invasively with a validated oscillometric device. The SBP/MET slope was calculated and the threshold for an eBPR was set at > 6.2 mmHg/MET. Two groups were defined according to ≤ 6.2 and > 6.2 mmHg/MET, and associations of CBP and vascular function with the SBP/MET slope were compared for each group. RESULTS: Athletes with an eBPR (n = 180, 29%) displayed a significantly higher systolic CBP (102.9 ± 7.5 vs. 100 ± 7.7 mmHg, p = 0.001) but a lower absolute (295 ± 58 vs. 384 ± 68 W, p < 0.001) and relative workload (3.14 ± 0.54 vs. 4.27 ± 1.1 W/kg, p < 0.001) compared with athletes with a normal SBP/MET slope (n = 438, 71%). Systolic CBP was positively associated with the SBP/MET slope (r = 0.243, p < 0.001). In multiple logistic regression analyses, systolic CBP (odds ratio [OR] 1.099, 95% confidence interval [CI] 1.045-1.155, p < 0.001) and left atrial volume index (LAVI) (OR 1.282, CI 1.095-1.501, p = 0.002) were independent predictors of an eBPR. CONCLUSION: Systolic CBP and LAVI were independent predictors of an eBPR. An eBPR was further associated with a lower performance level, highlighting the influence of vascular function on the BPR and performance of male elite athletes.

Echocardiographic pressure-strain loop-derived stroke work of the right ventricle: validation against the gold standard.

AIMS: Commercially available integrated software for echocardiographic measurement of stroke work (SW) is increasingly used for the right ventricle, despite a lack of validation. We sought to assess the validity of this method [echo-based myocardial work (MW) module] vs. gold-standard invasive right ventricular (RV) pressure-volume (PV) loops. METHODS AND RESULTS: From the prospectively recruiting EXERTION study (NCT04663217), we included 42 patients [34 patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) and 8 patients with absence of cardiopulmonary disease] with RV echocardiography and invasive PV catheterization. Echocardiographic SW was assessed as RV global work index (RVGWI) generated via the integrated pressure-strain MW software. Invasive SW was calculated as the area bounded by the PV loop. An additional parameter derived from the MW module, RV global wasted work (RVGWW), was correlated with PV loop measures. RVGWI significantly correlated with invasive PV loop-derived RV SW in the overall cohort [rho = 0.546 (P < 0.001)] and the PAH/CTEPH subgroup [rho = 0.568 (P < 0.001)]. Overall, RVGWW correlated with invasive measures of arterial elastance (Ea), the ratio of end-systolic elastance (Ees)/Ea, and end-diastolic elastance (Eed) significantly. CONCLUSIONS: Integrated echo measurement of pressure-strain loop-derived SW correlates with PV loop-based assessment of RV SW. Wasted work correlates with invasive measures of load-independent RV function. Given the methodological and anatomical challenges of RV work assessment, evolution of this approach by incorporating more elaborated echo analysis data and an RV reference curve might improve its reliability to mirror invasively assessed RV SW.

Fibroblast growth factor 23 as a biomarker of right ventricular dysfunction in pulmonary hypertension.

BACKGROUND: Fibroblast growth factor 23 (FGF-23) has been associated with left ventricular hypertrophy (LVH) and heart failure. However, its role in right ventricular (RV) remodeling and RV failure is unknown. This study analyzed the utility of FGF-23 as a biomarker of RV function in patients with pulmonary hypertension (PH). METHODS: In this observational study, FGF-23 was measured in the plasma of patients with PH (n = 627), dilated cardiomyopathy (DCM, n = 59), or LVH with severe aortic stenosis (n = 35). Participants without LV or RV abnormalities served as controls (n = 36). RESULTS: Median FGF-23 plasma levels were higher in PH patients than in healthy controls (p < 0.001). There were no significant differences between PH, DCM, and LVH patients. Analysis across tertiles of FGF-23 levels in PH patients revealed an association between higher FGF-23 levels and higher levels of NT-proBNP and worse renal function. Furthermore, patients in the high-FGF-23 tertile had a higher pulmonary vascular resistance (PVR), mean pulmonary artery pressure, and right atrial pressure and a lower cardiac index (CI) than patients in the low tertile (p < 0.001 for all comparisons). Higher FGF-23 levels were associated with higher RV end-diastolic diameter and lower tricuspid annular plane systolic excursions (TAPSE) and TAPSE/PASP. Receiver operating characteristic analysis revealed FGF-23 as a good predictor of RV maladaptation, defined as TAPSE < 17 mm and CI < 2.5 L/min/m2. Association of FGF-23 with parameters of RV function was independent of the glomerular filtration rate in regression analysis. CONCLUSION: FGF-23 may serve as a biomarker for maladaptive RV remodeling in patients with PH.

Normative values of non-invasively assessed RV function and pulmonary circulation coupling for pre-participation screening derived from 497 male elite athletes.

BACKGROUND: Reference values for right ventricular function and pulmonary circulation coupling were recently established for the general population. However, normative values for elite athletes are missing, even though exercise-related right ventricular enlargement is frequent in competitive athletes. METHODS: We examined 497 healthy male elite athletes (age 26.1 ± 5.2 years) of mixed sports with a standardized transthoracic echocardiographic examination. Tricuspid annular plane excursion (TAPSE) and systolic pulmonary artery pressure (SPAP) were measured. Pulmonary circulation coupling was calculated as TAPSE/SPAP ratio. Two age groups were defined (18-29 years and 30-39 years) and associations of clinical parameters with the TAPSE/SPAP ratio were determined and compared for each group. RESULTS: Athletes aged 18-29 (n = 349, 23.8 ± 3.5 years) displayed a significantly lower TAPSE/SPAP ratio (1.23 ± 0.3 vs. 1.31 ± 0.33 mm/mmHg, p = 0.039), TAPSE/SPAP to body surface area (BSA) ratio (0.56 ± 0.14 vs. 0.6 ± 0.16 mm*m2/mmHg, p = 0.017), diastolic blood pressure (75.6 ± 7.9 vs. 78.8 ± 10.7 mmHg, p < 0.001), septal wall thickness (10.2 ± 1.1 vs. 10.7 ± 1.1 mm, p = 0.013) and left atrial volume index (27.5 ± 4.5 vs. 30.8 ± 4.1 ml/m2, p < 0.001), but a higher SPAP (24.2 ± 4.5 vs. 23.2 ± 4.4 mmHg, p = 0.035) compared to athletes aged 30-39 (n = 148, 33.1 ± 3.4 years). TAPSE was not different between the age groups. The TAPSE/SPAP ratio was positively correlated with left ventricular stroke volume (r = 0.133, p = 0.018) and training amount per week (r = 0.154, p = 0.001) and negatively correlated with E/E' lat. (r = -0.152, p = 0.005). CONCLUSION: The reference values for pulmonary circulation coupling determined in this study could be used to interpret and distinguish physiological from pathological cardiac remodeling in male elite athletes.

CILP1 as a biomarker for right ventricular dysfunction in patients with ischemic cardiomyopathy.

The aim of this study was to evaluate the cartilage intermediate layer protein 1 (CILP1) as a biomarker of right ventricular dysfunction in patients with ischemic cardiomyopathy (ICM). CILP1 plasma concentrations were measured in 98 patients with ICM and 30 controls without any cardiac abnormalities. All participants underwent cardiac magnetic resonance imaging. Median CILP1 concentrations were higher in ICM than in controls. In the tertile analysis, low right ventricular ejection fraction (RVEF) and high right ventricular end-systolic volume index and N-terminal pro-brain natriuretic peptide (NT-proBNP) were associated with higher CILP1 levels in ICM. However, there were no associations between CILP1 concentrations and left ventricular (LV) parameters in this group. In receiver-operating characteristic (ROC) analysis CILP1 was a good predictor of RVEF < 40% with an optimal cut-off value of 3545 pg/ml in ICM, whereas it was not predictive of LV ejection fraction (LVEF) < 40% (area under the curve [AUC] = 0.57) There was no significant difference between the ROC curves of CILP1 (AUC = 0.72) and NT-proBNP (AUC = 0.77) for RVEF < 40% (p = 0.42). In multivariable regression analysis, RVEF was the only independent predictor of elevated CILP1. CILP1 and LVEF were the only independent predictors of RVEF < 40% in ICM. Our analysis demonstrates the potential role of CILP1 as a novel cardiac biomarker of prognostically relevant RV dysfunction in patients with ICM.

Vascular alterations among male elite athletes recovering from SARS-CoV-2 infection.

SARS-CoV-2 may affect the cardiovascular system and vascular impairment has been reported in healthy young adults recovering from COVID-19. However, the impact of SARS-CoV-2 infection on the vascular function of elite athletes is unknown. We examined 30 healthy male elite athletes (age 25.8 ± 4.6 years) pre-season and at a 6-month follow-up (182 ± 10 days). Vascular function and central blood pressure were calculated using transfer function-based analysis of peripheral arterial waveforms obtained by oscillometry. We performed a two-way repeated-measures ANOVA on the biomarker data, with SARS-CoV-2 status as the between-groups factor and time as the within-groups factor. Subjects who tested positive for SARS-CoV-2 were studied 18 ± 4 days after their positive testing date at follow-up. Of 30 athletes, 15 tested positive for SARS-CoV-2 after the first examination and prior to the follow-up. None had severe COVID-19 or reported any persisting symptoms. The results of the two-way repeated measures ANOVA revealed that there was no significant main effect of COVID-19 on any of the investigated biomarkers. However, there was a significant interaction between the effects of SARS-CoV-2 exposure and time on augmentation index (Aix) (p = 0.006) and augmentation index normalized to a heart rate of 75 beats per minute (Aix@75), (p = 0.0018). The observation of an interaction effect on Aix and Aix@75 in the absence of any main effect indicates a cross-over interaction. Significant vascular alterations in male elite athletes recovering from COVID-19 were observed that suggest vascular impairment. Whether these alterations affect athletic performance should be evaluated in future studies.

Relevance of Cor Pulmonale in COPD With and Without Pulmonary Hypertension: A Retrospective Cohort Study.

BACKGROUND: The relevance of cor pulmonale in COPD and pulmonary hypertension due to COPD (PH-COPD) is incompletely understood. We aimed to investigate the relationship of right ventricular-pulmonary arterial (RV-PA) uncoupling with disease severity in COPD, and the relationship of RV-PA uncoupling and use of targeted PH therapies with mortality in PH-COPD. METHODS: We retrospectively analyzed 231 patients with COPD without PH and 274 patients with PH-COPD. COPD was classified according to GOLD stages and the modified Medical Research Council dyspnoea scale. PH was categorized as mild-to-moderate or severe. RV-PA uncoupling was assessed as the echocardiographic tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio. RESULTS: Of the cohort with COPD without PH, 21, 58, 54 and 92 were classified as GOLD I, II, III and IV, respectively. Patients in advanced GOLD stages and those with severe dyspnoea showed significantly decreased TAPSE/PASP.Of the PH-COPD cohort, 144 had mild-to-moderate PH and 130 had severe PH. During follow-up, 126 patients died. In univariate Cox regression, TAPSE/PASP and 6-min walk distance (6MWD; 10 m increments) predicted survival [hazard ratios (95% CI): 0.12 (0.03-0.57) and 0.95 (0.93-0.97), respectively]; notably, PH severity and simplified European Society of Cardiology/European Respiratory Society risk stratification did not. Among patients in the lowest or intermediate tertiles of TAPSE/PASP and 6MWD, those with targeted PH therapy had higher survival than those without (53 vs. 17% at 3 years). CONCLUSION: Cor pulmonale (decreased TAPSE/PASP and 6MWD) is associated with disease severity in COPD and predicts outcome in PH-COPD.

GDF-15 and soluble ST2 as biomarkers of right ventricular dysfunction in pulmonary hypertension.

Background: This study analyzed the utility of soluble ST2 (sST2) and GDF-15 as biomarkers of right ventricular (RV) function in patients with pulmonary hypertension (PH). Methods: GDF-15 and sST2 serum concentrations were measured in patients with PH (n = 628), dilated cardiomyopathy (n = 31) and left ventricular hypertrophy (n = 47), and in healthy controls (n = 61). Results: Median sST2 and GDF-15 levels in patients with left ventricular hypertrophy were higher than in patients with PH and dilated cardiomyopathy. In tertile analysis GDF-15 >1363 pg/ml and sST2 >38 ng/ml were associated with higher N-terminal pro-brain natriuretic peptide, RV systolic dysfunction, RV-pulmonary arterial uncoupling and hemodynamic impairment. Conclusion: GDF-15 and sST2 are potential biomarkers of RV dysfunction in patients with PH.

Application and Validation of the Tricuspid Annular Plane Systolic Excursion/Systolic Pulmonary Artery Pressure Ratio in Patients with Ischemic and Non-Ischemic Cardiomyopathy.

The main aim of this study was to assess the prognostic utility of TAPSE/PASP as an echocardiographic parameter of maladaptive RV remodeling in cardiomyopathy patients using cardiac magnetic resonance (CMR) imaging. Furthermore, we sought to compare TAPSE/PASP to TAPSE. The association of the echocardiographic parameters TAPSE/PASP and TAPSE with CMR parameters of RV and LV remodeling was evaluated in 111 patients with ischemic and non-ischemic cardiomyopathy and cut-off values for maladaptive RV remodeling were defined. In a second step, the prognostic value of TAPSE/PASP and its cut-off value were analyzed regarding mortality in a validation cohort consisting of 221 patients with ischemic and non-ischemic cardiomyopathy. A low TAPSE/PASP (<0.38 mm/mmHg) and TAPSE (<16 mm) were associated with a lower RVEF and a long-axis RV global longitudinal strain (GLS) as well as higher RVESVI, RVEDVI and NT-proBNP. A low TAPSE/PASP, but not TAPSE, was associated with a lower LVEF and long-axis LV GLS, and a higher LVESVI, LVEDVI and T1 relaxation time at the interventricular septum and the RV insertion points. Furthermore, in the validation cohort, low TAPSE/PASP was associated with a higher mortality and TAPSE/PASP was an independent predictor of mortality. TAPSE/PASP is a predictor of maladaptive RV and LV remodeling associated with poor outcomes in cardiomyopathy patients.

Osteopontin and galectin-3 as biomarkers of maladaptive right ventricular remodeling in pulmonary hypertension.

Aim: This study assessed the utility of osteopontin (OPN) and galectin-3 (Gal-3) as biomarkers of maladaptive right ventricular remodeling in pulmonary hypertension (PH). Materials & methods: We examined plasma levels of OPN and Gal-3 in patients with PH (n = 62), dilated cardiomyopathy (n = 34), left ventricular hypertrophy (LVH; n = 47), and controls without right ventricle (RV) or LV abnormalities (n = 38). Results: OPN and Gal-3 levels were higher in PH, dilated cardiomyopathy and LVH than in the controls. OPN concentrations in PH patients with maladaptive RV were significantly higher than in those with adaptive RV. Gal-3 did not differentiate between adaptive and maladaptive RV remodeling in PH. OPN and Gal-3 levels did not correlate with parameters of LV remodeling. Conclusion: OPN is a potential biomarker of RV maladaptation.

Latest Developments in Robotic Percutaneous Coronary Intervention.

Interventional cardiovascular medicine has seen constant progress over the last few decades. Since the first angiograms and percutaneous transluminal coronary angioplasty were carried out, this progress has been tremendous and has led to a substantial decline in cardiovascular morbidity and mortality. The purpose of this article is to report and review the latest developments and evidence in robotics-assisted percutaneous coronary intervention (rPCI) and its potential future applications, opportunities, and limitations. Contemporary evidence shows that rPCI can lead to a significant reduction in radiation exposure as well as medical hazards for cardiologists. Rates of device and procedural success remain high and there is no evidence of a disadvantage for the patient. The accuracy of implantation with a reduced geographic mismatch is a further advantage that can result in a higher quality of treatment. Even in complex coronary lesions and procedures, rPCI seems to be safe and efficient. The latest developments include telestenting over hundreds of kilometers from a remote platform. Currently, the main limitations are the absence of large-scale randomized trials for the valid assessment of the benefits and disadvantages of rPCI as well as the technical limitations of the currently available rPCI systems. rPCI is a forward-looking innovation in cardiology that is applicable to a wide range of coronary interventions. Despite the present lack of knowledge and the limited data concerning the outcome for the patient, the available literature reveals promising results that should lead to improvements for physicians and patients.

Blood Pressure Response and Vascular Function of Professional Athletes and Controls.

Workload-indexed blood pressure response (wiBPR) to exercise has been shown to be superior to peak systolic blood pressure (SBP) in predicting mortality in healthy men. Thus far, however, markers of wiBPR have not been evaluated for athletes and the association with vascular function is unclear. We examined 95 male professional athletes (26±5 y) and 30 male controls (26±4 y). We assessed vascular functional parameters at rest and wiBPR with a graded bicycle ergometer test and compared values for athletes with those of controls. Athletes had a lower pulse wave velocity (6.4±0.9 vs. 7.2±1.5 m/s, p=0.001) compared to controls. SBP/Watt slope (0.34±0.13 vs. 0.44±0.12 mmHg/W), SBP/MET slope (6.2±1.8 vs. 7.85±1.8 mmHg/MET) and peak SBP/Watt ratio (0.61±0.12 vs. 0.95±0.17 mmHg/W) were lower in athletes than in controls (p<0.001). The SBP/Watt and SBP/MET slope in athletes were comparable to the reference values, whereas the peak SBP/Watt-ratio was lower. All vascular functional parameters measured were not significantly correlated to the wiBPR in either athletes or controls. In conclusion, our findings indicate the potential use of the SBP/Watt and SBP/MET slope in pre-participation screening of athletes. Further, vascular functional parameters, measured at rest, were unrelated to the wiBPR in athletes and controls.

CILP1 as a biomarker for right ventricular maladaptation in pulmonary hypertension.

The aim of our study was to analyse the protein expression of cartilage intermediate layer protein (CILP)1 in a mouse model of right ventricular (RV) pressure overload and to evaluate CILP1 as a biomarker of cardiac remodelling and maladaptive RV function in patients with pulmonary hypertension (PH).Pulmonary artery banding was performed in 14 mice; another nine mice underwent sham surgery. CILP1 protein expression was analysed in all hearts using Western blotting and immunostaining. CILP1 serum concentrations were measured in 161 patients (97 with adaptive and maladaptive RV pressure overload caused by PH; 25 with left ventricular (LV) hypertrophy; 20 with dilative cardiomyopathy (DCM); 19 controls without LV or RV abnormalities)In mice, the amount of RV CILP1 was markedly higher after banding than after sham. Control patients had lower CILP1 serum levels than all other groups (p<0.001). CILP1 concentrations were higher in PH patients with maladaptive RV function than those with adaptive RV function (p<0.001), LV pressure overload (p<0.001) and DCM (p=0.003). CILP1 showed good predictive power for maladaptive RV in receiver operating characteristic analysis (area under the curve (AUC) 0.79). There was no significant difference between the AUCs of CILP1 and N-terminal pro-brain natriuretic peptide (NT-proBNP) (AUC 0.82). High CILP1 (cut-off value for maladaptive RV of ≥4373 pg·mL-1) was associated with lower tricuspid annular plane excursion/pulmonary artery systolic pressure ratios (p<0.001) and higher NT-proBNP levels (p<0.001).CILP1 is a novel biomarker of RV and LV pathological remodelling that is associated with RV maladaptation and ventriculoarterial uncoupling in patients with PH.

[Chronic coronary syndrome]. / Chronisches Koronarsyndrom.

The 2019 guidelines of the European Society of Cardiology (ESC) rename stable coronary heart disease to chronic coronary syndrome (CCS). Under CCS, six different scenarios have been defined, which take its heterogeneity into account. An important part of the current guideline plays the diagnostic assessment of the pre-test probability in the event of the possible presence of stenosing coronary heart disease. The addition of dyspnea and clinical probability as additional variables for better estimation of the pre-test probability are two important new features. Imaging techniques such as CT angiography have been significantly upgraded as diagnostic procedures for the detection of CHD, while exercise ECG is no longer routinely recommended in this regard. Invasive coronary angiography with revascularization option remains a central diagnostic and therapeutic procedure. In addition to antianginal, lipid-lowering and antithrombotic therapy, the current CCS guideline places special emphasis on prevention by means of lifestyle modification.

SPARCL1 as a biomarker of maladaptive right ventricular remodelling in pulmonary hypertension.

Aim: This study assessed the utility of SPARC-like protein 1 (SPARCL1) as a biomarker of maladaptive right ventricular (RV) function in patients with pulmonary hypertension (PH).Methods: In this prospective study, we examined SPARCL1 levels in 105 patients with adaptive (n = 34) and maladaptive RV (n = 32) pressure overload caused by PH, dilated cardiomyopathy (DCM, n = 18) with LVEF < 35% and preserved RV function and controls without LV or RV abnormalities (n = 21).Results: The median SPARCL1 concentration in patients with maladaptive RV function was higher than in those with adaptive RV function (p < 0.01), DCM (p < 0.001) or controls (p < 0.001). Patients with adaptive RV function had higher SPARCL1 concentrations than controls (p < 0.05), whereas there was no difference between adaptive RV and DCM. SPARCL1 showed good predictive power for maladaptive RV (AUC 0.77, p < 0.001) with an optimal cut-off value of 9.66 ng/ml. The TAPSE/PASP ratio was the only independent predictor of SPARCL1 ≥ 9.66 ng/ml in multivariable logistic regression analysis.Conclusion: SPARCL1 shows potential as novel biomarker of RV pathological remodelling and is associated with RV maladaptation and ventriculoarterial uncoupling in PH.

Fractional flow reserve and frequency of PCI in patients with coronary artery disease.

BACKGROUND: Fractional flow reserve (FFR) guided percutaneous coronary intervention (PCI) has been validated in patients with stable coronary artery disease (CAD) but has not yet been verified under specific conditions such as heart failure or microvascular dysfunction. The aim of the present study was to examine the influence of specific patient comorbidities on FFR values and thus the frequency of PCI in patients with intermediate coronary stenosis. METHODS: A total of 652 patients with CAD and intermediate coronary stenosis who were assessed for FFR were included in this retrospective study. In a subgroup analysis, specific comorbidities such as heart failure with non-ST-segment-elevated acute coronary syndrome (NSTE-ACS), heart failure, diabetes mellitus, atrial fibrillation (AF), and left ventricular hypertrophy (LVH) were considered. RESULTS: In all lesions with an FFR ≤ 0.80 (n = 227/808, 28.1%), PCI was performed using drug-eluting stents. Pathological FFR values (FFR ≤ 0.80) before PCI were most frequently observed in the left anterior descending artery (LAD; n = 168/418, 39.9%) followed by the right coronary artery (RCA; n = 37/178, 20.7%) and the left circumflex artery (LCX; 22/223, 9.8%). The comorbidities NSTE-ACS (p = 0.28), heart failure with reduced ejection fraction (HFrEF; p = 0.63), heart failure with preserved ejection fraction (HFpEF; p = 0.3719), diabetes mellitus (p = 0.177), or LVH (p = 0.407) had no major impact on the occurrence of pathological FFR values; there was also no association between FFR and the occurrence of lesions in the different target vessels. CONCLUSION: The occurrence of pathological FFR values, most frequently documented in the LAD, was the same in patients with or without HFrEF, HFpEF, diabetes mellitus, AF, and LVH, demonstrating that these comorbidities did not influence FFR values and, thus, the indication for PCI.

Predictive value of preprocedural procalcitonin for short- and long-term mortality after transfemoral transcatheter aortic valve implantation.

Current risk scores used for patients undergoing transcatheter aortic valve implantation (TAVI) do not reliably predict adverse events after TAVI. Procalcitonin (PCT) is associated with increased atherosclerotic burden and adverse outcomes in patients with cardiovascular disease. The aim of our study is to assess the predictive value of preprocedural serum PCT levels in comparison with established risk scores in TAVI patients. A total of 243 patients undergoing transfemoral TAVI at our institution were included prospectively in the study and 230 of these patients participated in the follow-up 1 year after TAVI. The primary endpoints were mortality at 30 days and 1 year. Multivariable analysis revealed that preprocedural PCT was the only independent predictor of 30-day mortality (HR 2.84; 95% CI 1.59-5.06; p < 0.001) and 1-year mortality (HR 1.90; 95% CI 1.17-3.11; p = 0.01), whereas high-sensitivity C-reactive protein showed no association with procedural outcomes. The results of ROC analysis showed good predictive power of PCT for both outcomes (AUC 0.75; p = 0.0003 for 30-day mortality and AUC 0.71; p < 0.0001 for 1-year mortality). An optimal cut-off value for PCT of 0.06 ng/ml for short- and long-term mortality was determined with the Youden index. A significantly higher mortality rate was observed in the high-PCT group (≥ 0.06 ng/ml) based on Kaplan-Meier analysis (log rank = 12.1; p = 0.001 at 30 days and log rank = 14.2; p = 0.0002 at 1 year). Patients in the high-PCT group also had a considerably worse clinical pro6file. In conclusion, preprocedural PCT is an independent predictor of 30-day and 1-year mortality after TAVI. In particular, a cut-off value of 0.06 ng/ml discriminates patients at higher risk of mortality within 30 days and 1 year of TAVI.

Inducible cardiomyocyte-specific deletion of CaM kinase II protects from pressure overload-induced heart failure.

CaM kinase II (CaMKII) has been suggested to drive pathological cardiac remodeling and heart failure. However, the evidence provided so far is based on inhibitory strategies using chemical compounds and peptides that also exert off-target effects and followed exclusively preventive strategies. Therefore, the aim of this study was to investigate whether specific CaMKII inhibition after the onset of cardiac stress delays or reverses maladaptive cardiac remodeling and dysfunction. Combined genetic deletion of the two redundant CaMKII genes δ and γ was induced after the onset of overt heart failure as the result of pathological pressure overload induced by transverse aortic constriction (TAC). We used two different strategies to engineer an inducible cardiomyocyte-specific CaMKIIδ/CaMKIIγ double knockout mouse model (DKO): one model bases on tamoxifen-inducible mER/Cre/mER expression under control of the cardiac-specific αMHC promoter; the other strategy bases on overexpression of Cre recombinase via cardiac-specific gene transfer through adeno-associated virus (AAV9) under control of the cardiac-specific myosin light chain promoter. Both models led to a substantial deletion of CaMKII in failing hearts. To approximate the clinical situation, CaMKII deletion was induced 3 weeks after TAC surgery. In both models of DKO, the progression of cardiac dysfunction and interstitial fibrosis could be slowed down as compared to control animals. Taken together, we show for the first time that "therapeutic" CaMKII deletion after cardiac damage is sufficient to attenuate maladaptive cardiac remodeling and to reverse signs of heart failure. These data suggest that CaMKII inhibition is a promising therapeutic approach to combat heart failure.