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1.
Clin Res Cardiol ; 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33219854

RESUMO

AIMS: During the COVID-19 pandemic, hospital admissions for cardiac care have declined. However, effects on mortality are unclear. Thus, we sought to evaluate the impact of the lockdown period in central Germany on overall and cardiovascular deaths. Simultaneously we looked at catheterization activities in the same region. METHODS AND RESULTS: Data from 22 of 24 public health-authorities in central Germany were aggregated during the pandemic related lockdown period and compared to the same time period in 2019. Information on the total number of deaths and causes of death, including cardiovascular mortality, were collected. Additionally, we compared rates of hospitalization (n = 5178) for chronic coronary syndrome (CCS), acute coronary syndrome (ACS), and out of hospital cardiac arrest (OHCA) in 26 hospitals in this area. Data on 5,984 deaths occurring between March 23, 2020 and April 26, 2020 were evaluated. In comparison to the reference non-pandemic period in 2019 (deaths: n = 5832), there was a non-significant increase in all-cause mortality of 2.6% [incidence rate ratio (IRR) 1.03, 95% confidence interval (CI) 0.99-1.06; p = 0.16]. Cardiovascular and cardiac mortality increased significantly by 7.6% (IRR 1.08, 95%-CI 1.01-1.14; p = 0.02) and by 11.8% (IRR 1.12, 95%-CI 1.05-1.19; p < 0.001), respectively. During the same period, our data revealed a drop in cardiac catherization procedures. CONCLUSION: During the COVID-19-related lockdown a significant increase in cardiovascular mortality was observed in central Germany, whereas catherization activities were reduced. The mechanisms underlying both of these observations should be investigated further in order to better understand the effects of a pandemic-related lockdown and social-distancing restrictions on cardiovascular care and mortality.

2.
J Am Coll Cardiol ; 76(21): 2436-2446, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33213722

RESUMO

BACKGROUND: Current guidelines recommend intensified platelet inhibition by prasugrel or ticagrelor in patients with unstable angina (UA) or non-ST-segment elevation (NSTE) myocardial infarction (MI). OBJECTIVES: This study sought to investigate the benefits and risks of ticagrelor as compared with prasugrel in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and planned invasive management. METHODS: This post hoc analysis combines the pre-specified subgroups of UA and NSTEMI of the randomized ISAR-REACT 5 trial. It included 1,179 patients assigned to ticagrelor and 1,186 assigned to prasugrel. Ticagrelor was started immediately after randomization and prasugrel after coronary angiography. The primary endpoint was a composite of death, MI, or stroke during 1-year follow-up, and the safety endpoint was Bleeding Academic Research Consortium class 3-5. RESULTS: The primary endpoint was reached in 101 (8.7%) patients in the ticagrelor and in 73 (6.3%) patients in the prasugrel group (hazard ratio [HR]: 1.41; 95% confidence interval [CI]: 1.04 to 1.90). The HR for all-cause death was 1.43 (95% CI: 0.93 to 2.21) and that for MI 1.43 (95% CI: 0.94 to 2.19). The safety endpoint occurred in 49 (5.2%) patients in the ticagrelor and in 41 (4.7%) patients in the prasugrel group (HR: 1.09; 95% CI: 0.72 to 1.65). Landmark analysis revealed persistence of the efficacy advantage with prasugrel after the first month. CONCLUSIONS: In patients with NSTE-ACS, we found that prasugrel was superior to ticagrelor in reducing the combined 1-year risk of death, MI, and stroke without increasing the risk of bleeding. Due to the post hoc nature of the analysis, these findings need confirmation by further studies. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome; NCT01944800).

3.
JACC Cardiovasc Interv ; 13(22): 2642-2654, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33213749

RESUMO

OBJECTIVES: This study sought to compare patient characteristics, procedural outcomes, and valve hemodynamics of surgical aortic valve replacement (SAVR) with current-generation rapid-deployment valves (RDVs) versus transcatheter aortic valve replacement (TAVR) with current-generation transcatheter heart valves (THVs). BACKGROUND: The patient population currently treated with RDVs may have potential similarities with the current TAVR population, but comparative studies in a large patient population remain scarce. METHODS: A total of 16,473 patients who underwent isolated SAVR using current-generation RDVs or isolated transfemoral TAVR with current-generation THVs between 2011 and 2017 were enrolled into the German Aortic Valve Registry. Baseline, procedural, and in-hospital outcome parameters were analyzed for RDVs and THVs before and after 1:1 propensity score matching. Furthermore, RDVs and THVs with similar design characteristics were compared with each other. RESULTS: A total of 1,743 patients received SAVR with an RDV, whereas 14,730 patients were treated with transfemoral TAVR. Patients treated with TAVR were significantly older and had higher surgical risk scores. Following valve replacement, patients treated with an RDV had a significantly higher rate of disabling stroke (1.7% vs. 1.1%; p = 0.03), need for transfusion of >4 red blood cell units (8.5% vs. 1.4%; p < 0.001), and new onset renal replacement therapy (1.9% vs. 1.2%; p = 0.01), whereas the need for a new permanent pacemaker was lower (8.4% vs. 14.9%; p < 0.001). In-hospital mortality was similar (1.6% vs. 1.8%; p = 0.62). These findings persisted after 1:1 propensity score matching, but in-hospital mortality was significantly higher after RDVs (1.7% vs. 0.6%; p = 0.003). Balloon-expandable (BE) RDVs had significantly lower residual gradients compared with BE-THVs, while self-expanding (SE)-RDVs had significantly higher residual gradients compared with SE-THVs. CONCLUSIONS: In a large all-comers' registry, TAVR with current-generation THVs was associated with improved in-hospital outcomes compared with SAVR with current-generation RDVs. The pacemaker rate is significantly higher with TAVR. Post-procedural hemodynamic function varied between individual RDVs and THVs.

4.
Eur Respir J ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33184116

RESUMO

The aim of our study was to analyse the protein expression of cartilage intermediate layer protein 1 (CILP1) 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 9 mice underwent sham surgery. CILP1 protein expression was analysed in all hearts by 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 ROC analysis (AUC 0.79). There was no significant difference between the AUCs of CILP1 and NT-pro-BNP (AUC 0.82). High CILP1 (≥cut-off value for maladaptive RV of 4373 pg·mL-1) was associated with lower TAPSE/PASP ratios (p<0.001) and higher NT-pro-BNP 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.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33175478

RESUMO

OBJECTIVES: To compare the predictive performances of the prewiring, postwiring MI-SYNTAX scores, prewiring, and postwiring Updated Logistic Clinical SYNTAX score (LCSS) for 2-year all-cause mortality post percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) patients. BACKGROUND: In patients with STEMI and undergoing primary PCI, coronary stenosis(es) distal to the culprit lesion is often observed after the restoration of coronary flow. To address comprehensively the complex coronary anatomy in these patients, prewiring and postwiring MI-SYNTAX scores have been reported in the literature. Furthermore, to enable individualized risk estimation for long-term all-cause mortality, the Updated LCSS has been developed by combining the anatomical SYNTAX score and clinical factors. METHODS: In the randomized GLOBAL LEADERS trial, anatomical SYNTAX score analysis was performed by an independent angiographic corelab for the first 4,000 consecutive patients as a prespecified analysis; of these, 545 presented with STEMI. The efficacy of the mortality predictions of the four scores at 2 years were evaluated based on their discrimination and calibration abilities. RESULTS: Complete data was available in 512 patients (93.9%). When the patients were stratified into two groups based on the median of the scores, the prewiring and postwiring Updated LCSSs demonstrated that the high-score groups were associated with higher rates of 2-year all-cause mortality compared to the low-score groups (6.6 vs. 1.2%; log-rank p = .001 and 6.6 vs. 1.2%; log-rank p = .001, respectively). There were no statistically significant differences for predicting the mortality between the prewiring (area under the curve [AUC] 0.625), postwiring MI-SYNTAX score (AUC 0.614), prewiring (AUC 0.755), and postwiring Updated LCSS (AUC 0.757). In the integrated discrimination improvement (IDI), the prewiring MI-SYNTAX score had a better discrimination for the mortality than the postwiring MI-SYNTAX score (IDI -0.0082; p = .029). The four scores had acceptable calibration abilities for 2-year all-cause mortality. CONCLUSIONS: The prewiring Updated LCSS predicts long-term all-cause mortality with clearly useful discrimination and acceptable calibration. Since the postwiring MI-SYNTAX score does not improve mortality prediction, the prewiring MI-SYNTAX score may be preferred for the 2-year mortality prediction using the Updated LCSS.

6.
Herz ; 2020 Oct 12.
Artigo em Alemão | MEDLINE | ID: mdl-33044563

RESUMO

BACKGROUND: Renal sodium-glucose cotransporter­2 (SGLT2) inhibitors seem to have a cardioprotective effect beyond the antidiabetic effect. The underlying mechanisms are unclear. METHODS: Selective search in PubMed with a focus on heart failure endpoints and possible mechanisms of action. RESULTS: During treatment with three of the substances analyzed, there were fewer hospitalizations for heart failure compared with placebo; however, the numbers needed to treat within the primary analyses were relatively high (72-117). We found that loss of weight and lowering of blood pressure were more pronounced during treatment with verum than with placebo and an association of the preventive effect with more severely impaired renal function. CONCLUSION: The SGLT2 inhibitors show a moderate heart failure protective effect in diabetic patients. It is likely that a nephroprotective effect with modulation of the cardiorenal interaction is an important part of the mechanism of action but this must be substantiated in further investigations.

7.
Cardiovasc Diabetol ; 19(1): 179, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33066794

RESUMO

BACKGROUND: Patients with both diabetes mellitus (DM) and chronic kidney disease (CKD) are a subpopulation characterized by ultrahigh ischemic and bleeding risk after percutaneous coronary intervention. There are limited data on the impact of ticagrelor monotherapy among these patients. METHODS: In this post hoc analysis of the GLOBAL-LEADERS trial, the treatment effects of the experimental (one-month dual-antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) versus the reference regimen (12-month DAPT followed by 12-month aspirin alone) were analyzed according to DM/CKD status. The primary endpoint was a composite endpoint of all-cause death or new Q-wave myocardial infarction at 2-years. The patient-oriented composite endpoint (POCE) was defined as the composite of all-cause death, any stroke, site-reported MI and any revascularization, whereas net adverse clinical events (NACE) combined POCE with BARC type 3 or 5 bleeding events. RESULTS: At 2 years, the DM + /CKD + patients had significantly higher incidences of the primary endpoint (9.5% versus 3.1%, adjusted HR 2.16; 95% CI [1.66-2.80], p < 0.001), BARC type 3 or 5 bleeding events, stroke, site-reported myocardial infraction, all revascularization, POCE, and NACE, compared with the DM-/CKD- patients. Among the DM + /CKD + patients, after adjustment, there were no significant differences in the primary endpoints between the experimental and reference regimen; however, the experimental regimen was associated with lower rates of POCE (20.6% versus 25.9%, HR 0.74; 95% CI [0.55-0.99], p = 0.043, pinteraction = 0.155) and NACE (22.7% versus 28.3%, HR 0.75; 95% CI [0.56-0.99], p = 0.044, pinteraction = 0.310), which was mainly driven by a lower rate of all revascularization, as compared with the reference regimen. The landmark analysis showed that while the experimental and reference regimen had similar rates of all the clinical endpoints during the first year, the experimental regimen was associated with significantly lower rates of POCE (5.8% versus 11.0%, HR 0.49; 95% CI [0.29-0.82], p = 0.007, pinteraction = 0.040) and NACE (5.8% versus 11.2%, HR 0.48; 95% CI [0.29-0.82], p = 0.007, pinteraction = 0.013) in the second year. CONCLUSION: Among patients with both DM and CKD, ticagrelor monotherapy was not associated with lower rates of all-cause death or new Q-wave, or major bleeding complications; however, it was associated with lower rates of POCE and NACE. These findings should be interpreted as hypothesis-generating. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT01813435).

8.
Eur Heart J ; 41(37): 3533-3545, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33085967

RESUMO

AIMS : The aim of this study was to determine the effect of ticagrelor monotherapy on clinically relevant bleeding and major ischaemic events in relation to clinical presentation with and without non-ST elevation acute coronary syndromes (NSTE-ACS) among patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES). METHODS AND RESULTS : We conducted a pre-specified subgroup analysis of The Ticagrelor With Aspirin or Alone in High Risk Patients After Coronary Intervention (TWILIGHT) trial, which enrolled 9006 patients with high-risk features undergoing PCI with DES. After 3 months of dual antiplatelet therapy (DAPT) with ticagrelor plus aspirin, 7119 adherent and event-free patients were randomized in a double-blind manner to ticagrelor plus placebo versus ticagrelor plus aspirin for 12 months. The primary outcome was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding while the composite of all-cause death, myocardial infarction (MI), or stroke was the key secondary outcome. Among patients with NSTE-ACS (n = 4614), ticagrelor monotherapy reduced BARC 2, 3, or 5 bleeding by 53% [3.6% vs. 7.6%; hazard ratio (HR) 0.47; 95% confidence interval (CI) 0.36-0.61; P < 0.001) and in stable patients (n = 2503) by 24% (4.8% vs. 6.2%; HR 0.76; 95% CI 0.54-1.06; P = 0.11; nominal Pint = 0.03). Rates of all-cause death, MI, or stroke among those with (4.3% vs. 4.4%; HR 0.97; 95% CI 0.74-1.28; P = 0.84) and without (3.1% vs. 3.2%; HR 0.96; 95% CI 0.61-1.49; P = 0.85) NSTE-ACS were similar between treatment arms irrespective of clinical presentation (Pint = 0.96). CONCLUSION : Among patients with or without NSTE-ACS who have completed an initial 3-month course of DAPT following PCI with DES, ticagrelor monotherapy reduced clinically meaningful bleeding events without increasing ischaemic risk as compared with ticagrelor plus aspirin. The benefits of ticagrelor monotherapy with respect to bleeding events were more pronounced in patients with NSTE-ACS. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02270242.

9.
Circulation ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33115278

RESUMO

Background: Data on the comparative efficacy and safety of ticagrelor versus prasugrel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) are limited. We assessed the efficacy and safety of ticagrelor versus prasugrel in a head-to-head comparison in STEMI patients undergoing primary PCI. Methods: In this pre-specified subgroup analysis, we included 1653 patients with STEMI randomized to receive ticagrelor or prasugrel in the setting of the ISAR REACT-5 trial. The primary endpoint was the incidence of death, myocardial infarction or stroke at 1 year after randomization. The secondary endpoint was the incidence of bleeding defined as Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding at 1 year after randomization. Results: The primary endpoint occurred in 83 patients (10.1%) in the ticagrelor group and in 64 patients (7.9%) in the prasugrel group (hazard ratio [HR]=1.31; 95% confidence interval [CI] 0.95-1.82; P=0.10). One-year incidence of all-cause death (4.9% vs. 4.7%; P=0.83), stroke (1.3% vs. 1.0%; P=0.46) and definite stent thrombosis (1.8% vs. 1.0%; P=0.15) did not differ significantly in patients assigned to ticagrelor or prasugrel. One-year incidence of myocardial infarction (5.3% vs. 2.8%; HR=1.95 [1.18-3.23], P=0.010) was higher with ticagrelor than with prasugrel. BARC type 3 to 5 bleeding occurred in 46 patients (6.1%) in the ticagrelor group and in 39 patients (5.1%) in the prasugrel group (HR=1.22 [0.80-1.87]; P=0.36). Conclusions: In patients with STEMI undergoing primary PCI, there was no significant difference in the primary endpoint between prasugrel and ticagrelor. Ticagrelor was associated with a significant increase in the risk for recurrent myocardial infarction. Clinical Trial Registration: URL: https://www.clinicaltrials.gov; Unique identifier NCT01944800.

10.
Am J Cardiol ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33065080

RESUMO

Patients undergoing staged percutaneous coronary intervention (SPCI) are exposed to extended duration of antiplatelet therapy, and a novel aspirin-free antiplatelet regimen after SPCI should be specifically evaluated among these patients. This is a prespecified substudy of the GLOBAL LEADERS which is a randomized, open-label trial, comparing an experimental regimen of 1-month dual antiplatelet therapy (DAPT; ticagrelor and aspirin) followed by 23-month ticagrelor monotherapy to a reference regimen of 12-month DAPT followed by 12-month aspirin monotherapy. Patients were stratified according to whether or not SPCI was performed. The impact of the timing of SPCI on clinical outcomes was also investigated. Of 15,968 randomized patients, 1,651 patients underwent SPCI within 3 months. These patients with SPCI had a significantly higher risk of bleeding and ischemic endpoints than those without SPCI. In patients undergoing SPCI, the primary endpoint (composite of all-cause death or new Q-wave myocardial infarction at 2 years) and secondary safety endpoint (Bleeding Academic Research Consortium [BARC]-defined bleeding 3 or 5) were similar in the 2 regimens. However, in patients presenting with acute coronary syndrome (ACS), the experimental regimen reduced a risk of BARC 3 or 5 bleeding (1.8% vs 4.5%; HR 0.387; 95% CI 0.179 to 0.836; p = 0.016). In patients undergoing SPCI later than 10 days after index procedure, this risk reduction was still prominent (0.8% vs 2.3%; HR 0.321; 95% CI 0.116 to 0.891; p = 0.029). In conclusion, patients undergoing SPCI are at high risk and may need special attention from clinicians. In ACS patients undergoing SPCI, a novel aspirin-free antiplatelet regimen appears to be associated with a lower bleeding risk than with standard DAPT.

11.
JACC Cardiovasc Interv ; 13(19): 2238-2247, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33032712

RESUMO

OBJECTIVES: The aim of this study was to assess the efficacy and safety of ticagrelor versus prasugrel in patients with diabetes mellitus (DM) presenting with acute coronary syndromes (ACS) in whom invasive therapy was planned. BACKGROUND: The efficacy and safety of ticagrelor versus prasugrel in patients with ACS with DM undergoing invasive treatment remain unknown. METHODS: This pre-specified analysis of the ISAR-REACT (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment) 5 trial included 892 patients with ACS with DM and 3,124 patients with ACS without DM randomized to prasugrel or ticagrelor. The primary endpoint was a composite of death, myocardial infarction, or stroke; the safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding (both assessed 12 months after randomization). RESULTS: The primary endpoint occurred in 51 patients (11.2%) in the ticagrelor group and 55 patients (13.0%) in the prasugrel group in the DM cohort (hazard ratio: 0.84; 95% confidence interval: 0.58 to 1.24; p = 0.383) and in 132 patients (8.6%) in the ticagrelor group and 81 patients (5.2%) in the prasugrel group in the non-DM cohort (hazard ratio: 1.70; 95% confidence interval: 1.29 to 2.24; p < 0.001). There was a significant treatment arm-by-diabetic status interaction (pint = 0.0035). Bleeding Academic Research Consortium types 3 to 5 bleeding occurred in 27 patients (6.9%) in the ticagrelor group and 19 patients (5.5%) in the prasugrel group (p = 0.425) in the DM cohort and in 68 patients (5.2%) in the ticagrelor group and 60 patients (4.6%) in the prasugrel group in the non-DM cohort (p = 0.500). CONCLUSIONS: DM seems to affect the efficacy of ticagrelor and prasugrel in patients with ACS. In patients with DM, the efficacy of ticagrelor was comparable with that of prasugrel. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome [ISAR-REACT 5]; NCT01944800).

12.
Biomarkers ; : 1-10, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33045866

RESUMO

BACKGROUND: Whether Copeptin combined with high sensitivity troponin below the respective decision cut-offs improves rule-out of NSTEMI and may predict all-cause death at 30-day is under debate. METHODS: Data on 10,329 patients from 5 trials were pooled to evaluate the diagnostic and prognostic performance of an initial Copeptin below decision cut-off in combination with a (hs)-cTn below the uppler limit of normal (ULN) compared to a) the initial (hs)-cTn alone in the standard serial sampling strategy based on the 99th percentile and b) a single marker strategy (SMS) based on hs-cTn < limit of detection. Endpoints were sensitivities and negative predictive values (NPV) for rule-out of NSTEMI, 30-day all-cause mortality and rates of eligibility for DMS or SMS. RESULTS: NPV for NSTEMI was higher for DMS than for the initial cTn, regardless assay sensitivity. The highest NPVs were observed with DMS vs. hs-cTn (99.4% [95% CI: 99.0%-99.6%] vs. 98.8% [98.4%-99.1%],) , and improved performance was consistent across all important subgroups including presentation <3 h, again irrespective of assay sensitivity. The point estimate of all NPVs for all-cause death exceeded 99.75%. In the label populations, DMS versus SMS demonstrated comparably high NPVs for rule-out of NSTEMI (99.4% [99.0%-99.6%] vs. 99.9% [99.2%-100.0%]), very low mortality after rule-out (0.1% [0.0%-0.4% vs. 0.0% [0.0%-1.2%]), but eligibility for rule-out was 2.4-fold higher (61.4% [59.9%-62.9%] vs. 25.3% [23.7%-26.9%]) with DMS than SMS. CONCLUSION: Findings from a large pooled cohort corroborate the safety of the dual marker strategy for instant rule-out of NSTEMI, extending evidence to hs-cTn. Copeptin below cut-off in combination with hs-cTn below ULN may be used in more than 2.4-times more patients presenting with suspected ACS than a single marker strategy based on very low hs-cTn, without the need to exclude very early presenters or other important subgroups.

13.
Cardiovasc Res ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32960964

RESUMO

Many biomarkers that could be used to assess ejection fraction, heart failure, or myocardial infarction fail to translate into clinical practice because they lack essential performance characteristics or fail to meet regulatory standards for approval. Despite their potential, new technologies have added to the complexities of successful translation into clinical practice. Biomarker discovery and implementation requires a standardised approach that includes: identification of a clinical need; identification of a valid surrogate biomarker; stepwise assay refinement, demonstration of superiority over current standard-of-care; development and understanding of a clinical pathway; and demonstration of real-world performance. Successful biomarkers should improve efficacy or safety of treatment, while being practical at a realistic cost. Everyone involved in cardiovascular healthcare, including researchers, clinicians, and industry partners, are important stakeholders in facilitating the development and implementation of biomarkers. This paper provides suggestions for a development pathway for new biomarkers, discusses regulatory issues and challenges, and suggestions for accelerating the pathway to improve patient outcomes. Real life examples of successful biomarkers-high sensitivity cardiac troponin (hs-cTn), T2* cardiovascular magnetic resonance (CMR) imaging, and echocardiography-are used to illustrate the value of a standardised development pathway in the translation of concepts into routine clinical practice.

14.
Clin Res Cardiol ; 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32965556

RESUMO

OBJECTIVES: The aim of this study was to compare outcomes of transcatheter and surgical aortic valve implantation in chronic dialysis patients with aortic valve stenosis (AS). BACKGROUND: Chronic dialysis patients undergoing heart valve surgery are at higher risk for morbidity and mortality. Whether interventional techniques can reduce this risk is unclear because dialysis patients have thus far been excluded from randomized trials. METHODS: Chronic dialysis patients with AS enrolled in the German Aortic Valve Registry (GARY) between 2012 and 2015 were analyzed to compare transcatheter aortic valve implantation (TAVI n = 661) with surgical aortic valve replacement (SAVR n = 457). Propensity scores for inverse probability of treatment weighting (IPTW) were used to adjust the comparison of the two treatment groups for potential confounders. RESULTS: TAVI patients were older (78 ± 7.3 vs. 69 ± 10.2 years, p < 0.01, unadjusted) and had more comorbidities. Mortality at 1 year was the same (TAVI: 33.4% vs. SAVR 35.0%, p = 0.72, IPTW-adjusted) while it was lower with TAVI at 30 days (8.6% vs. 15.0%, p = 0.02, IPTW-adjusted). TAVI patients required more pacemaker implantation and showed more aortic regurgitation. SAVR patients required more blood transfusions and had longer hospital stay. Diabetes mellitus, atrial fibrillation, previous PCI, urgent procedure and EuroSCORE were associated with elevated 30-day mortality. Atrial fibrillation and older age were independent risk factor of 1-year mortality in both groups. CONCLUSIONS: Chronic dialysis patients with AS undergoing TAVI or SAVR had the same 1-year mortality, although survival at 30 days was better with TAVI. These results suggest that TAVI may improve peri-procedural outcomes.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32956446

RESUMO

AIMS: To investigate the efficacy and safety of ticagrelor monotherapy in patients undergoing percutaneous coronary intervention (PCI) stratified according to the baseline white blood cell (WBC) count. METHODS AND RESULTS: This is a post-hoc analysis of the GLOBAL LEADERS trial, a multicentre, open-label, randomized all-comer trial in patients undergoing PCI, comparing the experimental strategy (23-month ticagrelor monotherapy following 1-month dual anti-platelet therapy [DAPT]) with the reference strategy (12-month aspirin monotherapy following 12-month DAPT). Patients were stratified into two WBC groups, either < or ≥median WBC count of 7.8 x 109 cells/L (lower or higher WBC group, respectively). The primary endpoint was a composite of all-cause mortality or new Q-wave myocardial infarction (MI) at 2 years.Out of 14,576 patients included in the present study, 7,212 patients (49.5%) were classified as the lower WBC group, who had a significantly lower risk of both ischemic and bleeding outcomes at 2 years. At 2 years, the experimental strategy was associated with a significant lower incidence of the primary endpoint compared with the reference strategy in the lower WBC group (2.8% vs. 4.2%; hazard ratio [HR]: 0.67; 95% CI: 0.52-0.86) but not in the higher WBC group (4.8% vs. 4.7%; HR: 1.01; 95% CI: 0.82-1.25; pinteraction=0.013). There were no significant differences in the risks of BARC type 3 or 5 bleeding between two antiplatelet strategies regardless of the WBC groups. CONCLUSIONS: Increased WBC counts, which may reflect degree of inflammation, at the time of index procedure may attenuate the anti-ischemic benefits of ticagrelor monotherapy observed in patients with lower WBC counts.

16.
Clin Res Cardiol ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948882

RESUMO

BACKGROUND: The aim of this study was to assess the safety and effectiveness of intravascular lithotripsy (IVL) in treating eccentric calcified coronary lesions. METHODS: Between December 2015 and March 2019, 180 patients were enrolled in the Disrupt CAD I and CAD II studies across 19 sites in 10 countries. Patient-level data were pooled from these two studies (n = 180), within which 47 eccentric lesions (26%) and 133 concentric lesions were identified. RESULTS: Clinical success, defined as residual stenosis < 50% after stenting and no in-hospital MACE, was similar between the eccentric and concentric cohorts (93.6% vs. 93.2%, p = 1.0). There were no perforations, abrupt closure, slow flow or no reflow events observed in either group, and there were low rates of flow-limiting dissections (Grade D-F: 0% eccentric, 1.7% concentric; p = 0.54). Final acute gain and percent residual stenosis were similar between the two groups. Final residual stenosis of 8.6 ± 9.8% in eccentric and 10.0 ± 9.0% (p = 0.56) in concentric stenosis confirms the significant effect of IVL in calcified coronary lesions. CONCLUSION: In this first report from a pooled patient-level analysis of coronary IVL from the Disrupt CAD I and CAD II studies, IVL use was associated with consistent improvement in procedural and clinical outcomes in both eccentric and concentric calcified lesions.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32941620

RESUMO

AIMS: The 5-item PRECISE-DAPT, integrating age, haemoglobin, white-blood-cell count, creatinine clearance, and prior bleeding, predicts bleeding risk in patients on dual antiplatelet therapy (DAPT) after stent implantation. We sought to assess whether the bleeding risk prediction offered by the PRECISE-DAPT remains valid among patients receiving ticagrelor monotherapy from 1 month onwards after coronary stenting instead of standard DAPT and having or not having centrally-adjudicated bleeding endpoints. METHODS AND RESULTS: The PRECISE-DAPT was calculated in 14,928 and 7,134 patients from GLOBAL LEADERS and GLASSY trials, respectively. The ability of the score to predict BARC 3 or 5 bleeding was assessed and compared among patients on ticagrelor monotherapy (experimental strategy) or standard DAPT (reference strategy) from 1 month after drug-eluting stent implantation. Bleeding endpoints were investigator-reported or centrally-adjudicated in GLOBAL LEADERS and GLASSY, respectively.At 2 years, the c-indexes for the score among patients treated with the experimental or reference strategy were 0.67 (95% confidence interval [CI]:0.63-0.71) vs. 0.63 (95% CI:0.59-0.67) in GLOBAL LEADERS (p = 0.27), and 0.67 (95% CI:0.61-0.73) vs. 0.66 (95% CI:0.61-0.72) in GLASSY (p = 0.88). Decision curve analysis showed net benefit using the PRECISE-DAPT to guide bleeding risk assessment under both treatment strategies. Results were consistent between investigator-reported and adjudicated endpoints and using the simplified 4-item PRECISE-DAPT. CONCLUSIONS: The PRECISE-DAPT offers a prediction model that proved similarly effective to predict clinically-relevant bleeding among patients on ticagrelor monotherapy from 1 month after coronary stenting compared with standard DAPT and appears to be unaffected by the presence or absence of adjudicated bleeding endpoints.

18.
Int J Cardiol ; 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32941872

RESUMO

BACKGROUND: Despite the overall neutral results of the GLOBAL-LEADERS trial, results from a prespecified subgroup analysis showed that patients from Western Europe had a significantly lower rate of the primary endpoint when treated with ticagrelor monotherapy. Therefore, we aimed to examine the regional disparities in patients' baseline characteristics and their response to ticagrelor monotherapy. METHODS: Patients' baseline characteristics and the treatment effects of ticagrelor combined with aspirin for 1 month, followed by ticagrelor monotherapy for 23-months versus 12-months of standard dual antiplatelet therapy (DAPT) were compared according to participating countries. The primary endpoint was a composite endpoint of all-cause death or new Q-wave myocardial infarction at two years. RESULTS: Significant variances in patients' baseline characteristics were found between participating countries. The primary endpoint varied significantly according to the country (Pinteraction = 0.027). Patients from France (1.6% versus 5.2%, HR: 0.31, 95%CI: 0.13-0.73) and The Netherlands (2.4% versus 4.8%, HR, 0.50, 95%CI: 0.26-0.94) had lower rates of the primary endpoint when allocated to ticagrelor monotherapy, compared with the standard DAPT regimen. Of the 26 baseline and post-randomization factors explored, variance in the rate of complex PCI between countries was identified as the top contributor to this regional interaction. CONCLUSIONS: Patients' baseline characteristics varied between participating countries in the GLOBAL-LEADERS trial. There is a significant regional variance in the treatment effect of ticagrelor monotherapy, which could partly be explained by the differences in complex PCI being performed. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT01813435).

19.
Biomarkers ; 25(7): 578-586, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32901511

RESUMO

PURPOSE: This study examined sST2, GDF-15, and galectin-3 as indicators of disease severity and therapy response in chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: This study included 57 inoperable CTEPH patients who underwent balloon pulmonary angioplasty and 25 controls without cardiovascular disease. Biomarker levels were examined in relation to advanced hemodynamic impairment [tertile with worst right atrial pressure (RAP) and cardiac index], hemodynamic therapy response [normalized hemodynamics (meanPAP ≤25 mmHg, PVR ≤3 WU and RAP ≤6 mmHg) or a reduction of meanPAP ≥25%; PVR ≥ 35%, RAP ≥25%]. RESULTS: GDF-15 [820 (556-1315) pg/ml vs. 370 (314-516) pg/ml; p < 0.001] and sST2 [53.7 (45.3-74.1) ng/ml vs. 48.7 (35.5-57.0) ng/ml; p = 0.02] were higher in CTEPH patients than in controls. At baseline, a GDF-15 level ≥1443 pg/ml (AUC 0.88; OR 31.4) and a sST2 level ≥65 ng/ml (AUC 0.80; OR 10.9) were associated with advanced hemodynamic impairment. At follow-up GDF-15 ≤ 958 pg/ml (AUC = 0.74, OR 18) identified patients with optimal hemodynamic therapy response and ≤760 pg/ml (AUC = 0.79, OR 14). CONCLUSION: GDF-15 and sST2 levels are higher in CTEPH and identified patients with advanced hemodynamic impairment. Further, decreased GDF-15 levels at follow-up were associated with hemodynamic therapy response. The diagnostic strength was not superior to NT-proBNP.

20.
Dtsch Med Wochenschr ; 145(16): 1162-1168, 2020 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-32791553

RESUMO

Cardiac amyloidosis is a rare cause of cardiomyopathy, however, it is part of an underdiagnosed underlying systemic disease. For transthyretin (ATTR) amyloidosis, which is caused by the deposition of incorrectly folded transthyretin, either as the wild-type (wtATTR) or mutated (mATTR) form, novel evidence-based treatment options were recently shown to reduce disease progression as well as hospitalisation rates for heart failure. Thus, it is important to establish early and reliable diagnosis of cardiac involvement with ATTR amyloidosis.Modern non-invasive imaging (cardio magnetic resonance (CMR) and scintigraphic methods) together with immune fixation with determination of free light chains allow fast and reliable clinical screening for cardiac amyloidosis, whereas endomyocardial biopsy and genetics are used for confirmation of the underlying diagnosis. Interdisciplinary teams including hemato-oncology, neurology, nephrology in addition to cardiology are essential to enable personalized targeted treatment strategies.

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