Zsolt Piroth

Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease

BACKGROUND The preferred initial treatment for patients with stable coronary artery disease is the best available medical therapy. We hypothesized that in patients with functionally significant stenoses, as determined by measurement of fractional flow reserve (FFR), percutaneous coronary intervention (PCI) plus the best available medical therapy would be superior to the best available medical therapy alone. METHODS In patients with stable coronary artery disease for whom PCI was being considered, we assessed all stenoses by measuring FFR. Patients in whom at least one stenosis was functionally significant (FFR, ≤0.80) were randomly assigned to FFR-guided PCI plus the best available medical therapy (PCI group) or the best available medical therapy alone (medical-therapy group). Patients in whom all stenoses had an FFR of more than 0.80 were entered into a registry and received the best available medical therapy. The primary end point was a composite of death, myocardial infarction, or urgent revascularization. RESULTS Recruitment was halted prematurely after enrollment of 1220 patients (888 who underwent randomization and 332 enrolled in the registry) because of a significant between-group difference in the percentage of patients who had a primary end-point event: 4.3% in the PCI group and 12.7% in the medical-therapy group (hazard ratio with PCI, 0.32; 95% confidence interval [CI], 0.19 to 0.53; P<0.001). The difference was driven by a lower rate of urgent revascularization in the PCI group than in the medical-therapy group (1.6% vs. 11.1%; hazard ratio, 0.13; 95% CI, 0.06 to 0.30; P<0.001); in particular, in the PCI group, fewer urgent revascularizations were triggered by a myocardial infarction or evidence of ischemia on electrocardiography (hazard ratio, 0.13; 95% CI, 0.04 to 0.43; P<0.001). Among patients in the registry, 3.0% had a primary end-point event. CONCLUSIONS In patients with stable coronary artery disease and functionally significant stenoses, FFR-guided PCI plus the best available medical therapy, as compared with the best available medical therapy alone, decreased the need for urgent revascularization. In patients without ischemia, the outcome appeared to be favorable with the best available medical therapy alone. (Funded by St. Jude Medical; ClinicalTrials.gov number, NCT01132495.).

Fractional Flow Reserve–Guided PCI for Stable Coronary Artery Disease

BACKGROUND We hypothesized that in patients with stable coronary artery disease and stenosis, percutaneous coronary intervention (PCI) performed on the basis of the fractional flow reserve (FFR) would be superior to medical therapy. METHODS In 1220 patients with stable coronary artery disease, we assessed the FFR in all stenoses that were visible on angiography. Patients who had at least one stenosis with an FFR of 0.80 or less were randomly assigned to undergo FFR-guided PCI plus medical therapy or to receive medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy alone and were included in a registry. The primary end point was a composite of death from any cause, nonfatal myocardial infarction, or urgent revascularization within 2 years. RESULTS The rate of the primary end point was significantly lower in the PCI group than in the medical-therapy group (8.1% vs. 19.5%; hazard ratio, 0.39; 95% confidence interval [CI], 0.26 to 0.57; P<0.001). This reduction was driven by a lower rate of urgent revascularization in the PCI group (4.0% vs. 16.3%; hazard ratio, 0.23; 95% CI, 0.14 to 0.38; P<0.001), with no significant between-group differences in the rates of death and myocardial infarction. Urgent revascularizations that were triggered by myocardial infarction or ischemic changes on electrocardiography were less frequent in the PCI group (3.4% vs. 7.0%, P=0.01). In a landmark analysis, the rate of death or myocardial infarction from 8 days to 2 years was lower in the PCI group than in the medical-therapy group (4.6% vs. 8.0%, P=0.04). Among registry patients, the rate of the primary end point was 9.0% at 2 years. CONCLUSIONS In patients with stable coronary artery disease, FFR-guided PCI, as compared with medical therapy alone, improved the outcome. Patients without ischemia had a favorable outcome with medical therapy alone. (Funded by St. Jude Medical; FAME 2 ClinicalTrials.gov number, NCT01132495.).

Remote ischaemic postconditioning protects the heart during acute myocardial infarction in pigs

Background: Ischaemic preconditioning results in a reduction in ischaemic-reperfusion injury to the heart. This beneficial effect is seen both with direct local preconditioning of the myocardium and with remote preconditioning of easily accessible distant non-vital limb tissue. Ischaemic postconditioning with a comparable sequence of brief periods of local ischaemia, when applied immediately after the ischaemic insult, confers benefits similar to preconditioning. Objective: To test the hypothesis that limb ischaemia induces remote postconditioning and hence reduces experimental myocardial infarct size in a validated swine model of acute myocardial infarction. Methods: Acute myocardial infarction was induced in 24 pigs with 90 min balloon inflations of the left anterior descending coronary artery. Remote ischaemic postconditioning was induced in 12 of the pigs by four 5 min cycles of blood pressure cuff inflation applied to the lower limb immediately after the balloon deflation. Infarct size was assessed by measuring 72 h creatinine kinase release, MRI scan and immunohistochemical analysis. Results: Area under the curve of creatinine kinase release was significantly reduced in the postconditioning group compared with the control group with a 26% reduction in the infarct size (p<0.05). This was confirmed by MRI scanning and immunohistochemical analysis that revealed a 22% (p<0.05) and a 47.52% (p<0.01) relative reduction in the infarct size, respectively. Conclusion: Remote ischaemic postconditioning is a simple technique to reduce infarct size without the hazards and logistics of multiple coronary artery balloon inflations. This type of conditioning promises clear clinical potential.

Fractional Flow Reserve–Guided Multivessel Angioplasty in Myocardial Infarction

BACKGROUND In patients with ST‐segment elevation myocardial infarction (STEMI), the use of percutaneous coronary intervention (PCI) to restore blood flow in an infarct‐related coronary artery improves outcomes. The use of PCI in non‐infarct‐related coronary arteries remains controversial. METHODS We randomly assigned 885 patients with STEMI and multivessel disease who had undergone primary PCI of an infarct‐related coronary artery in a 1:2 ratio to undergo complete revascularization of non‐infarct‐related coronary arteries guided by fractional flow reserve (FFR) (295 patients) or to undergo no revascularization of non‐infarct‐related coronary arteries (590 patients). The FFR procedure was performed in both groups, but in the latter group, both the patients and their cardiologist were unaware of the findings on FFR. The primary end point was a composite of death from any cause, nonfatal myocardial infarction, revascularization, and cerebrovascular events at 12 months. Clinically indicated elective revascularizations performed within 45 days after primary PCI were not counted as events in the group receiving PCI for an infarct‐related coronary artery only. RESULTS The primary outcome occurred in 23 patients in the complete‐revascularization group and in 121 patients in the infarct‐artery‐only group that did not receive complete revascularization, a finding that translates to 8 and 21 events per 100 patients, respectively (hazard ratio, 0.35; 95% confidence interval [CI], 0.22 to 0.55; P<0.001). Death occurred in 4 patients in the complete‐revascularization group and in 10 patients in the infarct‐artery‐only group (1.4% vs. 1.7%) (hazard ratio, 0.80; 95% CI, 0.25 to 2.56), myocardial infarction in 7 and 28 patients, respectively (2.4% vs. 4.7%) (hazard ratio, 0.50; 95% CI, 0.22 to 1.13), revascularization in 18 and 103 patients (6.1% vs. 17.5%) (hazard ratio, 0.32; 95% CI, 0.20 to 0.54), and cerebrovascular events in 0 and 4 patients (0 vs. 0.7%). An FFR‐related serious adverse event occurred in 2 patients (both in the group receiving infarct‐related treatment only). CONCLUSIONS In patients with STEMI and multivessel disease who underwent primary PCI of an infarct‐related artery, the addition of FFR‐guided complete revascularization of non‐infarct‐related arteries in the acute setting resulted in a risk of a composite cardiovascular outcome that was lower than the risk among those who were treated for the infarct‐related artery only. This finding was mainly supported by a reduction in subsequent revascularizations. (Funded by Maasstad Cardiovascular Research and others; Compare‐Acute ClinicalTrials.gov number, NCT01399736.)

Five-Year Outcomes with PCI Guided by Fractional Flow Reserve

BACKGROUND We hypothesized that fractional flow reserve (FFR)–guided percutaneous coronary intervention (PCI) would be superior to medical therapy as initial treatment in patients with stable coronary artery disease. METHODS Among 1220 patients with angiographically significant stenoses, those in whom at least one stenosis was hemodynamically significant (FFR, ≤0.80) were randomly assigned to FFR‐guided PCI plus medical therapy or to medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy and were entered into a registry. The primary end point was a composite of death, myocardial infarction, or urgent revascularization. RESULTS A total of 888 patients underwent randomization (447 patients in the PCI group and 441 in the medical‐therapy group). At 5 years, the rate of the primary end point was lower in the PCI group than in the medical‐therapy group (13.9% vs. 27.0%; hazard ratio, 0.46; 95% confidence interval [CI], 0.34 to 0.63; P<0.001). The difference was driven by urgent revascularizations, which occurred in 6.3% of the patients in the PCI group as compared with 21.1% of those in the medical‐therapy group (hazard ratio, 0.27; 95% CI, 0.18 to 0.41). There were no significant differences between the PCI group and the medical‐therapy group in the rates of death (5.1% and 5.2%, respectively; hazard ratio, 0.98; 95% CI, 0.55 to 1.75) or myocardial infarction (8.1% and 12.0%; hazard ratio, 0.66; 95% CI, 0.43 to 1.00). There was no significant difference in the rate of the primary end point between the PCI group and the registry cohort (13.9% and 15.7%, respectively; hazard ratio, 0.88; 95% CI, 0.55 to 1.39). Relief from angina was more pronounced after PCI than after medical therapy. CONCLUSIONS In patients with stable coronary artery disease, an initial FFR‐guided PCI strategy was associated with a significantly lower rate of the primary composite end point of death, myocardial infarction, or urgent revascularization at 5 years than medical therapy alone. Patients without hemodynamically significant stenoses had a favorable long‐term outcome with medical therapy alone. (Funded by St. Jude Medical and others; FAME 2 ClinicalTrials.gov number, NCT01132495.)

Prognostic Value of Fractional Flow Reserve Measured Immediately After Drug-Eluting Stent Implantation.

Background— The predictive value of fractional flow reserve (FFR) measured immediately after percutaneous coronary intervention (PCI) with drug-eluting stent placement has not been prospectively investigated. We investigated the potential of post-PCI FFR measurements to predict clinical outcome in patients from FAME 1 and 2 trials (Fractional Flow Reserve or Angiography for Multivessel Evaluation). Methods and Results— All patients of FAME 1 and FAME 2 who had post-PCI FFR measurement were included. The primary outcome was vessel-oriented composite end point at 2 years, defined as vessel-related cardiovascular death, vessel-related spontaneous myocardial infarction, and ischemia-driven target vessel revascularization. Eight hundred thirty-eight vessels in 639 patients were analyzed. Baseline FFR values did not differ between vessels with versus without vessel-oriented composite end point (0.66±0.11 versus 0.63±0.14, respectively; P=0.207). Post-PCI FFR was significantly lower in vessels with vessel-oriented composite end point (0.88±0.06 versus 0.90±0.06, respectively; P=0.019). Comparing the 2-year outcome of lower and upper tertiles of post-PCI FFR significant difference was found favoring upper tertile in terms of overall vessel-oriented composite end point (9.2% versus 3.8%, respectively; hazard ratio, 1.46; 95% confidence interval, 1.02–2.08; P=0.037) and target vessel revascularization (7.0% versus 2.4%, respectively; hazard ratio, 1.59; 95% confidence interval, 1.03–2.46; P=0.037). When adjusted to sex, hypertension, diabetes mellitus, target vessel, serial stenosis, and baseline percentage diameter stenosis, a strong trend was preserved in terms of target vessel revascularization (harzard ratio, 1.55; 95% confidence interval, 0.97–2.46; P=0.066), favoring the upper tertile. Post-PCI FFR of 0.92 was found to have the highest diagnostic accuracy; however, the positive likelihood ratio remained low (<1.4). Conclusions— A higher post-PCI FFR value is associated with a better vessel-related outcome. However, its predictive value is too low to advocate its use as a surrogate clinical end point.

Drugs, gene transfer, signaling factors: a bench to bedside approach to myocardial stem cell therapy

In the past few years, the dogma that the heart is a terminally differentiated organ has been challenged. Evidence from preclinical investigations emerged that there are cells, even in the heart itself, that may be able to restore impaired cardiac function after myocardial infarction. Although the exact mechanisms by which the infarcted heart can be repaired by stem cells are not yet fully defined, there is a new optimism among cardiologists that this treatment will prove successful in addressing the cause of heart failure after myocardial infarction—myocyte loss. Despite the promising preliminary data of human myocardial stem cell trials, scientists have also focused on the possibility of enhancing the underlying mechanisms of stem cell repair to gain healthier myocardial tissue. Attempts to induce neo-angiogenesis by transfecting stem cells with signaling factors (such as VEGF), to raise the number of endothelial progenitor cells with medical treatments (such as statins), to transfect stem cells with heat shock protein 70 (as a cardioprotective agent against ischemia) and to enhance the healing process after myocardial infarction with the use of various forms of stimulating factors (G-CSF, SCF, GM-CSF) have been made with notable results. In this article, we summarize the evidence from preclinical and clinical myocardial stem cell studies that have addressed the possibility of enhancing the regenerative capacity of cells used after myocardial infarction.

Clinical value of post-percutaneous coronary intervention fractional flow reserve value: A systematic review and meta-analysis.

Background Fractional flow reserve (FFR) prior to percutaneous coronary intervention (PCI) is useful to guide treatment. Whether post‐PCI FFR assessment might have clinical impact is controversial. The aim of this study is to evaluate the range of post‐PCI FFR values and analyze the relationship between post‐PCI FFR and clinical outcomes. Methods We systematically searched the PubMed, EMBASE, and Cochrane Library databases with cross‐referencing of articles reporting post‐PCI FFR and correlating post‐PCI FFR values and clinical outcomes. The outcomes of interest were the immediate post‐PCI FFR values and the correlations between post‐PCI FFR and the incidence of repeat intervention and major adverse cardiac events (MACE). Results From 1995 to 2015, a total of 105 studies (n = 7470) were included, with 46 studies reporting post‐PCI FFR and 59 studies evaluating relationship between post‐PCI and clinical outcomes up to 30 months after PCI. Overall, post‐PCI FFR values demonstrated a normal distribution with a mean value of 0.90 ± 0.04. There was a positive correlation between the percentage of stent use and post‐PCI FFR (P < .0001). Meta‐regression analysis indicated that higher post‐PCI FFR values were associated with reduced rates of repeat intervention (P < .0001) and MACE (P = .0013). A post‐PCI FFR ≥0.90 was associated with significantly lower risk of repeat PCI (odds ratio 0.43, 95% CI 0.34‐0.56, P < .0001) and MACE (odds ratio 0.71, 95% CI 0.59‐0.85, P = .0003). Conclusions FFR measurement after PCI was associated with prognostic significance. Further investigation is required to assess the role of post‐PCI FFR and validate cutoff values in contemporary clinical practice.

Natriureticus peptidek mérése szívelégtelen betegekben: a helyes laboratóriumi és klinikai gyakorlat

Cardiac natriuretic peptides (BNP, NT-proBNP) play a pivotal role in cardiovascular homeostasis, mainly due to their roles in vasodilatation, natriuresis, diuresis and due to their antiproliferative properties. Proper measurement of the natriuretic peptide levels may help differentiate between respiratory and cardiac forms of dyspnea, diagnose early forms of heart failure, evaluate severity of heart failure (prognosis) and monitor the efficacy of therapy. In many countries natriuretic peptide levels are being used as one of the earliest diagnostics tools to evaluate the involvement of the heart. Current theoretical and clinical data confirm the importance of natriuretic peptides in routine healthcare. These roles are clearly described in international recommendations and guidelines. In the current review the authors discuss the problems of the measurement of natriuretic peptides in Hungary, including several aspects related to laboratory medicine, cardiology and health economy.

[Transient left ventricular apical akinesis with systolic dysfunction after physical exercise: a form of tako-tsubo syndrome].

A Gottsegen Gyorgy Orszagos Kardiologiai Intezet Koronariaőrzőjebe egy 43 eves, diabeteszes, hipertonias nőbeteg kerult felvetelre fizikai terhelest kovetően jelentkező tipusos mellkasi fajdalom, nehezlegzes miatt. A felveteli EKG-n anterior ST-elevatio latszott. Az azonnal elvegzett koronarografia ep epicardialis erstatuszt abrazolt. A szivultrahang csokkent szisztoles balkamra-funkciot mutatott az osszes csucsi szegmentum akinezisevel. A laborvizsgalatok csak enyhen emelkedett cTnI- es CKMB-ertekeket mutattak. A korhazi tartozkodast kovetően a beteget jo altalanos allapotban emittaltuk, a 4 het mulva megismetelt kepalkoto vizsgalatok soran csaknem teljesen normalis bal kamrai funkcio igazolodott szegmentalis falmozgaszavar nelkul. A fent ismertetett tunetegyuttes megfelel az irodalomban tako-tsubo-szindromakent ismert betegsegnek, amely ep koszoruerrendszer mellett jelentkező atmeneti csucsi falmozgaszavarral es bal kamrai diszfunkcioval jar. Irodalmi adatok alapjan a legvaloszinűbbnek tartott ok az eme...A 43-year-old woman with mild hypertension and type-2 diabetes mellitus was presented to the coronary care unit because of ongoing chest pain and associated dyspnea after physical exercise. On arrival, her ECG disclosed ST-segment elevations in the precordial leads. The emergent cardiac catheterization failed to demonstrate coronary artery disease. The prompt performed transthoracic echocardiogram demonstrated systolic dysfunction with apical ballooning. Akinetic segments were irrespective of coronary artery anatomy. Laboratory tests revealed only slightly elevated cardiac enzymes: we observed a significant discrepancy between the extent of akinesis and the minimal increase in cardiac necroenzymes. The patient was medically managed and discharged in stable condition, with follow-up at 4 weeks demonstrating nearly total recovery of cardiac function and total resolution of wall motion disorder. Her clinical presentation is consistent with that of tako-tsubo cardiomyopathy, a syndrome that is characterized by transient apical regional wall motion abnormalities in the absence of epicardial coronary artery disease. Main precipitating factor is thought to be the cathecolamin excess due to emotional or physical stress, subarachnoid hemorrhage, phaeochromocytoma or cocaine use. The authors report the first physical exercise induced tako-tsubo syndrome in the Hungarian medical literature.