Tünde Pintér

The impact of cardiopulmonary manifestations on the mortality of SSc: a systematic review and meta-analysis of observational studies

OBJECTIVES Internal organ involvement reduces the life expectancy of SSc patients. Cardiopulmonary manifestations are currently the primary cause of death. We aimed to perform a systematic review and meta-analysis to define more precise effect estimates of different cardiopulmonary manifestations and to verify trends in the mortality of SSc. METHODS A systematic literature search was performed to identify relevant cohort studies. Reports analyzing the role of the organ manifestations in mortality or analysing survival compared with the control population were included. The outcome parameters were pooled with the random-effect model via generic inverse-variance weighting in conventional and cumulative meta-analysis. RESULTS Eighteen studies comprising a total of 12, 829 patients qualified. The reported causes of death were as follows: 19.7% cardiac, 16.8% interstitial pulmonary disease, 13.1% pulmonary hypertension and 13.8% renal disease. The risk of death was significantly increased in patients with cardiac involvement [hazard ratio (HR) 3.15], with pulmonary interstitial disease (HR 2.58), with pulmonary hypertension (HR 3.50) and with renal manifestations (HR 2.76). A trend for survival improvement (R2)= 0.4295, P = 0.04) was found, and the difference in survival between the diffuse and limited scleroderma subgroups was diminishing (R2)= 0.4119. P = 0.02). CONCLUSION Meta-analysis of observational studies indicates a trend for improvement over the last decades in which the life expectancy of SSc patients approaches that of the general population. A decreasing tendency in the survival differences between the limited and diffuse SSc subgroups was also verified. Internal organ involvements have similarly unfavourable predictive impact on survival.

Justification of 150 mg clopidogrel in patients with high on-clopidogrel platelet reactivity.

Eur J Clin Invest 2012; 42 (4): 384–392

Overlap of coronary disease and pulmonary arterial hypertension in systemic sclerosis

Objectives: Pulmonary arterial hypertension (PAH) is a common complication of systemic sclerosis (SSc). Symptoms of coronary artery disease (CAD) and PAH are closely related and cardiac catheterisation is needed to confirm their diagnosis. The aim of the present work was to investigate of the extent of overlap between CAD and PAH in patients with SSc. Methods: Based on non-invasive investigations, 20 patients out of 120 were suspected to have PAH (“suspected PAH” group). Another 10 patients showed signs of coronary disease (“suspected CAD” Group). In these 30 patients, right heart catheterisation and coronary angiography were performed, and the coronary flow reserve (CFR) was assessed by thermodilution technique. Results: In the “suspected PAH” and the “suspected CAD” groups, PAH was found in 12/20 and 2/10 cases, and coronary artery stenosis in 9/20 and 6/10 cases, respectively. Severely reduced CFR was revealed in 7/20 and 3/10 cases, respectively. Conclusions: PAH, CAD and reduced CFR all show a considerable overlap in symptomatic patients with SSc. The current non-invasive investigations are neither sensitive nor specific enough to make an appropriate distinction between these different disease manifestations. A more invasive approach, such as coronary angiography at the initial catheterisation, is required to properly characterise and treat the different forms of cardiac involvement in SSc.

Thienopyridine Therapy Influences Late Outcome After Coronary Stent Implantation

Clinical significance of resistance to aspirin and thienopyridine therapy is poorly defined. The authors aimed to evaluate whether more effective antiplatelet therapy is associated with better outcome in patients on dual-antiplatelet treatment. Using optical aggregometer, maximal platelet aggregation values were measured with induction of adenosine diphosphate, collagen, and adrenaline 30 ± 5 days after coronary stent implantation in 134 patients. Markers of platelet activation were also analyzed with fluorescent immunoassay in 57 patients. After 10 months of follow-up, 33 patients reached the composite endpoint of cardiovascular death, myocardial infarction, and revascularisation. Adenosine diphosphate-induced maximal aggregation values were in significant relationship with the development of major adverse cardiac events (P < .01). Level of soluble P-selectin proved to be an independent risk factor of adverse outcome (P < .05). As efficacy of thienopyridine therapy showed significant relation with clinical outcome, the authors conclude that interindividual variability in response to adenosine diphosphate-receptor antagonists may be of substantial clinical importance.

Meta-analysis of randomized trials on access site selection for percutaneous coronary intervention in ST-segment elevation myocardial infarction.

Introduction Superior outcomes with transradial (TRPCI) versus transfemoral coronary intervention (TFPCI) in the setting of acute ST-segment elevation myocardial infarction (STEMI) have been suggested by earlier studies. However, this effect was not evident in randomized controlled trials (RCTs), suggesting a possible allocation bias in observational studies. Since important studies with heterogeneous results regarding mortality have been published recently, we aimed to perform an updated review and meta-analysis on the safety and efficacy of TRPCI compared to TFPCI in the setting of STEMI. Material and methods Electronic databases were searched for relevant studies from January 1993 to November 2012. Outcome parameters of RCTs were pooled with the DerSimonian-Laird random-effects model. Results Twelve RCTs involving 5,124 patients were identified. According to the pooled analysis, TRPCI was associated with a significant reduction in major bleeding (odds ratio (OR): 0.52 (95% confidence interval (CI) 0.38–0.71, p < 0.0001)). The risk of mortality and major adverse events was significantly lower after TRPCI (OR = 0.58 (95% CI: 0.43–0.79), p = 0.0005 and OR = 0.67 (95% CI: 0.52–0.86), p = 0.002 respectively). Conclusions Robust data from randomized clinical studies indicate that TRPCI reduces both ischemic and bleeding complications in STEMI. These findings support the preferential use of radial access for primary PCI.

Different Effect of IgA Nephropathy and Polycystic Kidney Disease on Arterial Stiffness

Background: Renal function is a major predictor of vascular function and cardiovascular diseases. Little information exists about the effect of specific renal diseases on vascular function in chronic kidney diseases (CKD). Methods: One hundred and twenty patients (60 with IgA nephropathy, IgAN, and 60 with polycystic kidney disease, PKD) with CKD stages 1–4 were studied and compared. Pulse-wave velocity was measured by the digital volume pulse (DVP) method and stiffness index (SIDVP) was derived. Results: All CKD (IgAN and PKD) patients had increased SIDVP compared to controls (10.39 vs. 8.87 ± 1.79 m/s, p = 0.008). PKD patients had increased SIDVP compared to IgAN and controls (11.14 ± 2.19, 9.66 ± 2.02 and 8.87 ± 1.79 m/s, respectively, p < 0.001). An inverse correlation was found between SIDVP and glomerular filtration rate in all CKD (IgAN and PKD) patients (p = 0.001) and in IgAN alone (p < 0.01), but not in PKD. With multivariate regression analysis, only age and 24-hour systolic blood pressure exerted independent effects on SIDVP. Conclusions: Compared to controls, arterial stiffness was increased in CKD patients. However, arterial stiffening was more pronounced in PKD than in IgAN, suggesting that vascular function is not similarly altered in etiologically different CKD groups. The fact that blood pressure was an independent risk factor underscores a therapeutic opportunity.

Mechanism of coronary flow reserve reduction in systemic sclerosis: insight from intracoronary pressure wire studies

OBJECTIVE Functional impairment of coronary microcirculation is thought to be a major pathway in the development of primary cardiac involvement in SSc; however, the underlying mechanism is not fully understood. We aimed to investigate the mechanisms of coronary flow reserve (CFR) reduction in patients with SSc. METHODS Seventeen SSc patients and 17 gender- and age-matched controls were enrolled. Coronary angiography and determination of coronary flow parameters including index of myocardial resistance (IMR) using intracoronary pressure wire at basal conditions and during vasodilator-induced maximal hyperaemia were performed. Transit times of repeated intracoronary saline injection were measured to evaluate the role of cold exposure. RESULTS SSc patients with decreased CFR had accelerated basal coronary flow velocity (P < 0.05), and their IMR in hyperaemia (IMR(hyp)) did not differ from either SSc patients with normal CFR or from the controls (P = 0.292 and P =  0.308). The coronary flow velocity of SSc patients correlated with the IMR at baseline (IMR(bas)) (r  = 0.56, P  = 0.019). Injection of room temperature saline did not provoke changes in coronary transit times. CONCLUSIONS The lack of decrease in the maximal vasodilatation response indicates that there is no irreversible functional damage at the level of the coronary arterioles. In patients with reduced CFR, the decreased basal IMR and higher velocity reflect compensatory vasodilatory mechanisms probably triggered by ischaemic signals deriving from abnormal myocardial microcirculation.

Justification of 150mg clopidogrel in patients with high on-clopidogrel platelet reactivity

Eur J Clin Invest 2012; 42 (4): 384–392

Clinical outcomes in patients treated for coronary in-stent restenosis with drug-eluting balloons: Impact of high platelet reactivity

Background The impact of high platelet reactivity (HPR) on clinical outcomes after elective percutaneous coronary interventions (PCI) with drug-eluting balloons (DEB) due to in-stent restenosis (ISR) is unknown. Objective We sought to evaluate the prognostic importance of HPR together with conventional risk factors in patients treated with DEB. Methods Patients treated with DEB due to ISR were enrolled in a single-centre, prospective registry between October 2009 and March 2015. Only patients with recent myocardial infarction (MI) received prasugrel, others were treated with clopidogrel. HPR was defined as an ADP-test >46U with the Multiplate assay and no adjustments were done based on results. The primary endpoint of the study was a composite of cardiovascular mortality, MI, any revascularization or stroke during one-year follow-up. Results 194 stable angina patients were recruited of whom 90% were treated with clopidogrel. Clinical characteristics and procedural data were available for all patients; while platelet function testing was performed in 152 subjects of whom 32 (21%) had HPR. Patients with HPR had a higher risk for the primary endpoint (HR: 2.45; CI: 1.01–5.92; p = 0.03). The difference was primarily driven by a higher risk for revascularization and MI. According to the multivariate analysis, HPR remained a significant, independent predictor of the primary endpoint (HR: 2.88; CI: 1.02–8.14; p = 0.04), while total DEB length and statin treatment were other independent correlates of the primary outcome. Conclusion HPR was found to be an independent predictor of repeat revascularization and MI among elective patients with ISR undergoing PCI with DEB.

PrasugRel versus adjusted high-dose clopidogrel in patients with high on- clopidogrel platelet reactivity: the PECS-HPR randomized, multicenter study

background: Repeated loading doses (LD) of clopidogrel were shown to effectively overcome high on-clopidogrel platelet reactivity (HPR); however, comparison to potent P2Y12-inhibitors is lacking. We sought to compare the antiplatelet effect of high-dose clopidogrel versus prasugrel at both short- and long-term in acute coronary syndrome patients (ACS) with HPR. methods: ACS patients receiving 600 mg clopidogrel pretreatment were randomized to prasugrel or high-dose clopidogrel in a multicenter, controlled trial if platelet function testing revealed HPR (>46U) after PCI. In the prasugrel group, patients received an immediate 60-mg LD followed by 10 mg for three days. After day 3, patients were randomized to either standard (10 mg) or reduced (5 mg) maintenance doses up to 30 days. Patients randomized to high-dose clopidogrel received repeated loading doses of 600 mg clopidogrel based on controlled platelet function testing for three days, then were randomized to 75 mg or 150 mg maintenance doses for 30 days. ADP-induced platelet reactivity was measured with the Multiplate assay at day 0 (randomization), 1, 2, 3 and 25. Results: Between May 2011 and March 2013, 147 patients were randomized. Although baseline platelet reactivity did not differ between groups (p=0.22), prasugrel provided significantly more rapid and more potent platelet inhibition compared to repeated LD-s of clopidogrel through all three days after randomization (p<0.0001). During the maintenance phase, there was a dose-dependent increase in platelet reactivity from prasugrel 10 mg to clopidogrel 75 mg (p for trend <0.0001), demonstrating the superiority of both doses of prasugrel over 75 and 150 mg clopidogrel. No difference was observed between clopidogrel groups at day 25 (p=0.35), leading to a rebound in HPR and returning to the level of baseline platelet reactivity with both 75 and 150 mg clopidogrel (p=0.66 vs. day 0). conclusion: Prasugrel provides significantly more rapid and more potent platelet reactivity inhibition compared to repeated loading doses of clopidogrel. The observed differences persisted with maintenance dosing, leading to rebound in HPR with both standard and high-dose clopidogrel.