A comprehensive and easy-to-use ECG algorithm to predict the coronary occlusion site in ST-segment elevation myocardial infarction.

BACKGROUND: Several electrocardiogram (ECG) criteria have been proposed to predict the location of the culprit occlusion in specific subsets of patients presenting with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to develop, through an independent validation of currently available criteria, a comprehensive and easy-to-use ECG algorithm, and to test its diagnostic performance in real-world clinical practice. METHODS: We analyzed ECG and angiographic data from 419 consecutive STEMI patients submitted to primary percutaneous coronary intervention over a one-year period, dividing the overall population into derivation (314 patients) and validation (105 patients) cohorts. In the derivation cohort, we tested >60 previously published ECG criteria, using the decision-tree analysis to develop the algorithm that would best predict the infarct-related artery (IRA) and its occlusion level. We further assessed the new algorithm diagnostic performance in the validation cohort. RESULTS: In the derivation cohort, the algorithm correctly predicted the IRA in 88% of cases and both the IRA and its occlusion level (proximal vs mid-distal) in 71% of cases. When applied to the validation cohort, the algorithm resulted in 88% and 67% diagnostic accuracies, respectively. In a real-world comparative test, the algorithm performed significantly better than expert physicians in identifying the site of the culprit occlusion (P = .026 vs best cardiologist and P < .001 vs best emergency medicine doctor). CONCLUSIONS: Derived from an extensive literature review, this comprehensive and easy-to-use ECG algorithm can accurately predict the IRA and its occlusion level in all-comers STEMI patients.

Myocardial Late Contrast Enhancement CT in Troponin-Positive Acute Chest Pain Syndrome.

Background Acute chest pain with mild troponin rise and inconclusive diagnosis after clinical evaluation represents a diagnostic challenge. Triple-rule-out (TRO) CT may exclude coronary artery disease (CAD), as well as acute aortic syndrome and pulmonary embolism, but cannot help identify other causes of myocardial injury. Purpose To investigate the diagnostic value of a comprehensive CT protocol including both an angiographic and a late contrast enhancement (LCE) scan in participants with troponin-positive acute chest pain. Materials and Methods In this prospective study, consecutive patients with troponin-positive acute chest pain or anginal equivalent and inconclusive diagnosis after clinical evaluation (symptoms, markers, electrocardiography, and echocardiography) who underwent TRO CT between June 2018 and September 2020 were enrolled. TRO CT was performed to evaluate the presence of obstructive CAD (stenosis ≥50%), acute aortic syndrome, and pulmonary embolism. If the findings on the TRO CT scan were negative, an LCE CT scan was acquired after 10 minutes to assess the presence and pattern of scar and quantify the myocardial extracellular volume fraction. CT-based diagnoses were compared with diagnoses obtained with reference standard methods, including invasive coronary angiography, cardiac MRI, and endomyocardial biopsy. Results Eighty-four patients (median age, 69 years [interquartile range, 50-77 years]; 45 men) were enrolled. TRO CT helped identify obstructive CAD in 35 participants (42%), acute aortic syndrome in one (1.2%), and pulmonary embolism in six (7.1%). LCE CT scans were acquired in the remaining 42 participants. The following diagnoses were reached with use of LCE CT: myocarditis (22 of 42 participants [52%]), takotsubo cardiomyopathy (four of 42 [10%]), amyloidosis (three of 42 [7.1%]), myocardial infarction with nonobstructed coronary arteries (three of 42 [7.1%]), dilated cardiomyopathy (two of 42 [4.8%]), and negative or inconclusive findings (eight of 42 [19%]). The addition of LCE CT improved the diagnostic rate of TRO CT from 42 of 84 participants (50% [95% CI: 38.9, 61.1]) to 76 of 84 (90% [95% CI: 82.1, 95.8]) (P < .001). Conclusion A CT protocol including triple-rule-out and late contrast enhancement CT scans improved diagnostic rate in participants presenting with acute chest pain syndrome. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Nagpal and Bluemke in this issue.

Transcatheter therapies for secondary mitral regurgitation in advanced heart failure: what are we aiming for?

A severe secondary mitral regurgitation (SMR) can be found in a significant portion of patients affected by advanced heart failure (AHF). Conventional therapies (optimal medical therapy, devices, surgery) present restricted clinical efficacy in this stage of the left ventricle disease which is burdened by high mortality and morbidity rates. Although the treatment of choice is represented by heart transplantation (HTx), there is an unmet need related to the limited supply of donor hearts (as opposed to the growing prevalence of AHF) and the low eligibility of highly symptomatic patients. In case of concomitant severe SMR, transcatheter mitral valve therapies (repair and replacement) may play a crucial role in this setting. While a direct prognostic improvement after correction of SMR has yet to be proved, AHF patients can benefit from the following: hemodynamic stabilization, symptomatic relief, normalization of pulmonary arterial pressures, and reduction in hospitalizations for acute heart failure. Obtaining these results may lead to the clinical consequences of reaching the HTx in good enough clinical status (bridge to heart transplantation), becoming eligible for the HTx (bridge to HTx candidacy), and being delisted for clinical improvement (bridge to recovery). Therefore, achieving traditional secondary endpoints in patients with AHF and SMR can translate into significant clinical implications.

Renal protection: a leading mechanism for cardiovascular benefit in patients treated with SGLT2 inhibitors.

Initially developed as glucose-lowering drugs, sodium-glucose co-transporter type 2 inhibitors (SGLT2i) have demonstrated to be effective agents for the risk reduction of cardiovascular (CV) events in patients with type 2 diabetes mellitus (T2DM). Subsequently, data has emerged showing a significant CV benefit in patients treated with SGLT2i regardless of diabetes status. Renal protection has been initially evaluated in CV randomized trials only as secondary endpoints; nonetheless, the positive results gained have rapidly led to the evaluation of nephroprotection as primary outcome in the CREDENCE trial. Different renal and vascular mechanisms can account for the CV and renal benefits enlightened in recent literature. As clinical guidelines rapidly evolve and the role of SGLT2i appears to become pivotal for CV, T2DM, and kidney disease management, in this review, we analyze the renal effects of SGLT2, the benefits derived from its inhibition, and how this may result in the multiple CV and renal benefits evidenced in recent clinical trials.

Amiodarone in ventricular arrhythmias: still a valuable resource?

Ventricular arrhythmias still represent an important cause of morbidity and mortality, especially in patients with heart failure and reduced left ventricular ejection fraction. Amiodarone is a Class III Vaughan-Williams anti-arrhythmic drug widely used in ventricular arrhythmias for its efficacy and low pro-arrhythmogenic effect. On the other hand, a significant limitation in its use is represented by toxicity. In this review, the pharmacology of the drug is discussed to provide the mechanistic basis for its clinical use. Moreover, all the latest evidence on its role in different clinical settings is provided, including the prevention of sudden cardiac death, implanted cardioverter defibrillators, ischemic and non-ischemic cardiomyopathies. A special focus is placed on everyday clinical practice learning points, such as dosage, indications, and contraindications from the latest guidelines.

Cardiac and sudden death after chronic total occlusion percutaneous coronary intervention: Prognostic role of the target vessel.

BACKGROUND: The role of the target vessel in percutaneous revascularization of chronic total occlusion (CTO) is unclear. OBJECTIVE: We sought to assess the long-term results of percutaneous coronary intervention (PCI) for CTO lesions in each coronary artery and to investigate the impact of successful revascularization and previous myocardial infarction (MI) in the territory of the target vessel. METHODS AND RESULTS: Cohort observational study on 1,124 patients who have undergone CTO PCI attempt: 371 on left anterior descending artery (LAD), 485 right coronary artery, and 268 left circumflex. Patients were further stratified by successfully revascularized and not-revascularized CTO (CTO-NR). Vessels affected by a previous MI were defined as infarct-related artery (IRA). The primary endpoint was cardiac death; the secondary endpoint was the combined rate of sudden cardiac-death and sustained ventricular-arrhythmias (SCD/SVAs). Propensity score-matching was performed to evaluate LAD versus NON-LAD CTO. Up to 12-year follow-up, the clinical benefit associated with successful PCI was consistent across the three groups. CTO-NR had the greatest association with cardiac death and SCD/SVAs in each coronary artery and in IRA-CTO patients. CONCLUSIONS: Unsuccessful percutaneous CTO revascularization was associated with lower cardiac survival and freedom from SCD/SVAs, irrespective of the vessel treated. This result was mainly driven by patients with an IRA CTO.

Long-term clinical effects of recanalization of chronic coronary total occlusions in patients with left ventricular systolic dysfunction.

OBJECTIVES: The aim of the present analysis is to evaluate the clinical impact of chronic total occlusions (CTOs) recanalization in patients with left ventricular (LV) systolic dysfunction. BACKGROUND: According to contemporary knowledge, patient selection for percutaneous CTO revascularization is not yet standardized. In particular, data on outcomes in patients with LV systolic dysfunction undergoing percutaneous coronary intervention (PCI) for CTO are scarce. METHODS: From a total of 2,421 consecutive patients with at least one CTO, 436 patients with ejection fraction (EF) ≤45%, who were referred for coronary angiography between January 1998 and September 2014, were selected. Patients with successful recanalization of the target CTO were assigned to CTO-revascularized group and those with failed or not attempted recanalization to the CTO-not revascularized (CTO-NR) group. Study endpoints were all-cause death, cardiac death, and occurrence of myocardial infarction on follow-up. RESULTS: Out of 436 CTO patients with reduced EF, 228 (52.3%) were successfully recanalized and 208 patients (47.7%) were not, either due to CTO-PCI failure (n = 106, 24.3%) or because CTO-PCI was not attempted (n = 102, 23.4%). At long-term follow-up, CTO-NR patients had significantly higher rate of overall (p = .021) and cardiac mortality (p = .035) compared to those successfully revascularized. CONCLUSION: In patients with systolic LV dysfunction (EF ≤ 45%), CTO revascularization was associated with significant lower rate of total and cardiac mortality compared to those with nonrevascularized CTO.

One-year clinical outcome of biodegradable polymer sirolimus-eluting stent in diabetic patients: Insight from the ULISSE registry (ULtimaster Italian multicenter all comerS Stent rEgistry).

BACKGROUND: The ULISSE registry evaluated the real-world performance of the Ultimaster® biodegradable polymer sirolimus-eluting stent (BP-SES) in a multicenter-independent cohort of patients undergoing percutaneous coronary intervention, including a large proportion of diabetes mellitus (DM) patients. METHODS: In this subgroup analysis, 1,660 consecutive patients, 2,422 lesions, treated with BP-SES enrolled in the ULISSE registry were divided in two groups: DM (485 patients, 728 lesions) and non-DM (1,175 patients, 1,694 lesions). Primary endpoint was target lesion failure (TLF), a composite endpoint of cardiac-death, target-vessel myocardial infarction (TV-MI), and clinically driven target lesion revascularization (TLR) at 1-year. Secondary endpoint was TLR at 1-year. RESULTS: At 1-year follow-up TLF occurred in 5% overall patients and was significantly higher in DM patients (8 vs. 3.7%; p = .001), due to more cardiac deaths (3.4 vs. 1.1%; p = .002). TLR occurred in 3.2% overall patients, and it was not significantly higher in DM compared to non-DM patients (4.4 vs. 2.8%; p = .114). The incidence of stent thrombosis was low and similar between groups (0.4 vs. 0.9%; p = .526). Insulin-treated DM (ITDM) patients showed higher rate of TLF as compared to non-ITDM patients (13 vs. 6.5%; p = .041), but similar rate of TLR (6 vs. 4%; p = .405). After adjustment for relevant comorbidities, DM was not significantly associated with TLF or cardiac death in patients undergoing BP-SES implantation. CONCLUSIONS: This study is the first all-comers evaluation of BP-SES in DM patients. Our findings show that DM patients, mostly those with ITDM, still represent a vulnerable population and experience significantly higher rate of TLF. Overall BP-SES efficacy is considerable, although not statistically significant higher rate of TLR is still present in DM compared to non-DM patients.

One-year clinical outcome of biodegradable polymer sirolimus-eluting stent in patients presenting with acute myocardial infarction: Insight from the ULISSE registry.

BACKGROUND: The ULISSE registry has demonstrated the real-world performance of the Ultimaster biodegradable polymer sirolimus-eluting stent (BP-SES) in a large cohort of patients undergoing percutaneous coronary intervention, including a large proportion of patients presenting with acute myocardial infarction (AMI). METHODS: We performed a subgroup analysis of the ULISSE registry in AMI patients and compared the outcomes of this vulnerable cohort with that of patients presenting without AMI (non-AMI). The primary end point was the incidence of 1-year target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction (TV-MI), and clinically indicated target lesion revascularization (TLR). RESULTS: Of 1,660 patients included in the ULISSE registry, 381(23%) presented with AMI, 207(54.3%) non-ST elevation myocardial infarction, and 174(45.7%) ST-elevation myocardial infarction. Compared with non-AMI patients, those with AMI were more frequently female and smokers, with lower left ventricular ejection fraction (LVEF) and chronic kidney disease requiring dialysis. At 1 year, TLF rate was significantly higher in AMI than non-AMI patients (7.9 vs. 4.1%; HR 1.98, CI 95% 1.22-3.23; p = .005) driven by higher rate of cardiac death (4.0 vs. 1.1%; HR 3.59, CI 95% 1.64-7.88; p = .01) and TV-MI (2.8 vs 0.9%; HR 2.99,CI 95% 1.22-7.37; p = .01), without differences in TLR rate (4.3 vs. 2.9%,HR 0.66, CI95% 0.35-1.25; p = .2). At multivariate Cox regression analysis, eGFR <40 mL/min (HR: 2.868) and LVEF <40% (HR: 2.394) were the only independent predictors of TLF. CONCLUSIONS: In AMI patients, Ultimaster BP-SES implantation was associated with higher rate of TLF and definite stent thrombosis compared with non-AMI patients. The high incidence of adverse events was mainly driven by the unfavorable baseline risk profile.

Real-Life Indications to Sacubitril/Valsartan Treatment in Patients With Chronic Systolic Heart Failure.

OBJECTIVE: International guidelines recommend the introduction of sacubitril/valsartan (Entresto) in patients with heart failure (HF) and reduced ejection fraction (EF), who remain symptomatic, despite optimal uptitrated therapy. The purpose of the following analysis is to verify the real-life eligibility for sacubitril/valsartan in a population of patients suffering from chronic HF, regularly monitored in a single HF clinic and treated according to guideline-directed medical therapy (GDMT). METHODS: From a total of 1070 patients regularly monitored in our HF Clinic between January 2011 and September 2017, the clinical records of 224 patients with HF and reduced EF on optimized GDMT were retrospectively analyzed. RESULTS: Of 224 analyzed patients, 75 improved their EF or were asymptomatic after uptitration of GDMT during follow-up; 50 were not on angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for different reasons; 13 patients had systolic blood pressure ≤100 mm Hg, so they were not eligible for sacubitril/valsartan introduction. The remaining patients were still symptomatic (NYHA ≥2), and therefore, sacubitril/valsartan introduction was indicated in these 86 patients (38.4%) of 224 enrolled. CONCLUSION: In patients with HF and reduced EF, where GDMT is appropriately achieved, indication to sacubitril/valsartan treatment is around 38%.

Echocardiographic features of post-transcatheter aortic valve implantation thrombosis and endocarditis.

BACKGROUND: Transcatheter heart valve thrombosis (THV-t) and endocarditis (THV-e) are relevant complications after transcatheter aortic valve implantation (TAVI). Transcatheter heart valve (THV) dysfunction definition is mostly based on Doppler (stenosis/regurgitation) without considering leaflets characteristics. PURPOSE: To evaluate the additional diagnostic value of leaflets echocardiographic features over Doppler when prosthetic valve complication is suspected. METHODS: Among 621 post-TAVI patients, 128 cases with probable valve complication were identified. THV-t was finally diagnosed in 13 patients (10%) and THV-e in 8 (6%), while the remaining 107 (84%) had no definitive diagnosis of thrombosis/endocarditis (THV-no). We analyzed at 2 time points (baseline and follow-up) both traditional Doppler parameters and leaflets morpho-functional features. RESULTS: Both Doppler and leaflets parameters showed high sensitivity (sensitivity 92%) and low specificity (ranging from specificity 32% to 74%) in detecting THV-t. Interestingly, the combination of mean aortic pressure gradient ≥20 mm Hg and leaflet thickening significantly improved the specificity of echocardiography for diagnosis of THV thrombosis (specificity 94%). On the other hand, echocardiographic diagnosis of THV endocarditis remained limited by very low sensitivity despite showing high specificity. CONCLUSIONS: The combination of Doppler and leaflets parameters can improve the echocardiographic diagnosis of THV thrombosis in post-TAVI patients with suspicious symptoms, via a significant increase in the overall test specificity. This would potentially allow more rational gatekeeping to more expensive/invasive diagnostic examinations (eg, CT scan) or therapeutic trials (eg, unnecessary anticoagulation).

Young Patient with Advanced Heart Failure No Longer a Candidate for Heart Transplantation after MitraClip® Procedure.

In Europe, mitral regurgitation (MR) is the second most common form of valvular heart disease requiring surgical treatment. The case is presented of a 36-year-old woman with end-stage heart failure secondary to chemotherapy-induced cardiotoxicity, complicated by severe MR. She was listed for heart transplantation and underwent percutaneous MitraClip® implantation in order to preclude further clinical deterioration while awaiting a suitable donor. The one-year follow-up showed a strong improvement of symptoms and mostly reverse left ventricular remodelling, with consequent removal from the heart transplantation list. Video 1: Four-chamber view at baseline. Video 2: Four-chamber view at one-year follow up. Video 3: Tricuspid regurgitation and right ventricle at baseline. Video 4: Tricuspid regurgitation and right ventricle at one-year follow up.

Predictors of restenosis following contemporary subintimal tracking and reentry technique: The importance of final TIMI flow grade.

OBJECTIVES: To identify predictors of restenosis after recanalization of chronic total occlusions (CTOs) with the Subintimal Tracking And Reentry (STAR) technique. BACKGROUND: STAR is associated with high rates of restenosis but the associated factors are not clear. Understanding the underlying mechanisms may be important to improve STAR outcomes and possibly other contemporary CTO recanalization techniques utilizing extensive subintimal dissection and stenting. METHODS: We retrospectively analyzed 211 lesions that underwent a STAR procedure (between 2002 and 2013) with a final Thrombolysis in Myocardial Infarction (TIMI) flow grade 2 or 3. One-hundred and nineteen lesions that received drug eluting stents (DES) and underwent follow-up angiography were included in the final analysis. RESULTS: Of the 119 lesions treated with DES following STAR, 75 restenoses were observed (63.0%). Utilizing multivariate analysis, TIMI flow grade in the recanalized artery following stent implantation at the end of the index procedure was the only independent predictor of restenosis. CONCLUSIONS: Following recanalization of a CTO with STAR, final TIMI flow predicted future restenosis or reocclusion. As a bailout technique, STAR resulted in a high acute success rate with good safety and acceptable long-term results. When poor flow is observed following recanalization, and prior to stent implantation, a two-step strategy whereby a second procedure is performed at an interval to maximize coronary flow at the end of the procedure may be considered with the goal to reduce the risk of future restenosis or total vessel occlusion following STAR.

PFO closure with only fluoroscopic guidance: 7 years real-world single centre experience.

AIMS: To evaluate the safety and the efficacy of fluoroscopy-guided only (Fluo-G) and of echocardiography-guided (Echo-G; trans-esophageal echocardiography-TEE-or intracardiac echocardiography-ICE) percutaneous closure of patent foramen ovale (PFO). METHODS AND RESULTS: Single center retrospective registry enrolling 368 consecutive patients (mean age 50.5 years) who underwent PFO closure between June 2004 and December 2011. Most patients had prior cryptogenic stroke (n = 126; 34.2%), TIA (n = 218; 51.1%); some of these had recurrent neurological events [multiple strokes n = 28 (7.8%); multiple TIAs n = 72 (18.6%)]. All the patients underwent a preprocedure TEE. PFO closure was performed with Echo-G in 187 patients (50.8%) (TEE n = 69, 36.8% and ICE n = 124, 66.3%). In Fluo-G cases, PFO with atrial septal aneurysm (ASA) was significantly less present (P < 0.005) and smaller devices (<25 mm) were implanted more frequently (P < 0.001). Both fluoroscopy and total procedural time were lower in the Fluo-G group (P < 0.0001). No differences were found in terms of successful device deployment (98.3% Fluo-G vs. 98.3% Echo-G) and RtL-shunt at follow-up (11.7% Fluo-G vs. 7.6% Echo-G). The rate of conversion from Fluoro-G to Echo-G procedure was 4.4% (n = 8). At a median follow-up of 4 years, freedom from recurrent embolic events rate was similar between the two groups (Echo-G 94.5 vs. Fluo-G 95.7%). CONCLUSIONS: In our experience Fluoro-G PFO closure was performed mainly in cases of simple anatomy, with similar results in terms of safety and efficacy compared to Echo-G cases. Both fluoroscopy and total procedural times were lower in the Fluo-G cases.

Coronary microvascular dysfunction in asymptomatic patients affected by systemic sclerosis - limited vs. diffuse form.

BACKGROUND: This observational study was designed to evaluate the prevalence of coronary microvascular dysfunction (CMD) in asymptomatic patients affected by systemic sclerosis (SSc), stratifying the results according to the limited (lcSSc) and the diffuse (dcSSc) forms of the disease. METHODS AND RESULTS: We enrolled 19 consecutive asymptomatic patients with dcSSc (n=7) or lcSSc (n=12). In all subjects, coronary flow reserve (CFR) was assessed by measuring diastolic coronary flow velocities in the left anterior descending artery by pulsed wave Doppler at baseline and after dipyridamole infusion (0.84 mg·kg(-1)·6 min(-1)). Wall motion score index was evaluated at baseline and during stress. We enrolled 20 healthy subjects as controls. Mean CFR was 1.96±0.62 in patients and 2.69±0.47 in controls (P<0.001). Abnormal values of CFR (≤2) were significantly more prevalent in patients than in controls (10/19 vs. 0/20; P<0.001) and in the dcSSc subgroup than in the lcSSc subgroup (6/7 vs. 4/12; P=0.05). An inverse relationship between disease duration (from time of onset of Raynaud's phenomenon) and CFR value was observed in the lcSSc group (correlation coefficient -0.583; P=0.046). Neither patients nor controls had wall motion abnormalities during dipyridamole administration. CONCLUSIONS: A blunted CFR, most likely because of CMD, is more frequent in patients affected by the dcSSc form in the early stages of the disease, whereas it seems to appear later in lcSSc.

Evidence of tricuspid valve remodeling in patients with severe mitral regurgitation independently of degree of functional tricuspid regurgitation: a two- and three-dimensional echocardiographic study.

BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate whether, in patients with severe mitral regurgitation (MR), tricuspid valve remodeling was independent of the degree of functional tricuspid regurgitation (FTR) present. Whether any differences in the analysis remodeling, as assessed by two-dimensional (2D) and three-dimensional (3D) echocardiography, can be demonstrated was also addressed. METHODS: A total of 188 patients (mean age 63.5 +/- 16.0 years) with severe organic or functional MR with or without associated FTR, and 30 normal controls (mean age 59.2 +/- 15 years) were enrolled in the study. Subsequently, both 2D and 3D transthoracic anatomic and functional parameters of the tricuspid valve were analyzed. RESULTS: Patients and controls differed in all 2D and 3D parameters of tricuspid valve remodeling, except for the 2D end-diastolic annular diameter and circularity indices. The patients were then allocated to either group A (trivial/mild FTR) or group B (moderate/severe FTR). Significant differences were identified between groups A and B compared to controls in all tricuspid valve remodeling indices, except for the diastolic 2D annular diameter and circularity indices. Groups A and B had similar 2D and 3D parameters of tricuspid valve remodeling. The right ventricular end-diastolic diameter (RVEDD) (beta = 0.24, 95% CI: 0.11 to 0.22, p = 0.02) and fractional area change (beta = -0.48, 95% CI: -0.24 to 0.09, p = 0.0001, R2 = 0.22) were independent predictors of the tenting area, whereas the RVEDD was the only independent predictor of the diastolic 3D tricuspid annular area (beta = 0.53, 95% CI: 1.2 to 2.7, p = 0.0001, R2 = 0.28). CONCLUSION: In patients with severe MR, tricuspid valve remodeling was also demonstrated in those with trivial/mild FTR, but was better characterized by 3D echocardiography. Tricuspid valve remodeling and right ventricular dilation were the main determinants of tricuspid valve regurgitation.

PlaCor PRT measurement of shear-activated platelet aggregate formation in stable patients treated with single and dual antiplatelet therapy.

Shear forces play a key role in thrombus formation and shear-based tests may better reflect physiological conditions in vivo compared with agonist-based tests. We evaluated the PlaCor PRT®, a novel platelet reactivity test based on shear-induced platelet aggregation, in patients with stable coronary artery disease (CAD) treated with single (SAPT) and dual antiplatelet therapy (DAPT). We examined 100 patients with multiple risk factors for CAD and/or documented stable CAD: 38 treated with SAPT, aspirin 100 mg qd, 62 treated with DAPT, aspirin 100 mg + clopidogrel 75 mg qd, compared with age- and sex-matched healthy volunteers without antiplatelet therapy (HV, n = 35). Measures of shear-induced platelet aggregation were performed with the PlaCor PRT®. In 25 patients in SAPT, the PlaCor test was also performed before and after a 12-hour-loading dose of clopidogrel 600 mg. The mean ± SD PRT time (seconds) in HV was 78 ± 13 and was significantly lower compared with SAPT (118 ± 16, p = 0.030) and to DAPT patients (242 ± 11, p < 0.0001). A statistically significant difference was also reported between SAPT and DAPT patients (p < 0.0001). After a loading dose of clopidogrel, the PRT time of SAPT patients increased significantly from 112 ± 20 to 254 ± 17, p < 0.0001. 2.7 and 26% of patients were considered as "poor responders" to single and dual antiplatelet therapy, respectively. This study shows that in patients with multiple risk factors for CAD and/or documented stable CAD, SAPT and DAPT play an important role in reducing platelet aggregation mediated by shear forces as evaluated with the novel PlaCor PRT®. Further studies will be required to confirm and assess the extent of these findings in patients with acute coronary syndromes.

[Metabolic therapy for heart failure]. / Terapia metabolica per l'insufficienza cardiaca.

Heart failure may promote metabolic changes such as insulin resistance, in part through neurohumoral activation, and determining an increased utilization of non-carbohydrate substrates for energy production. In fact, fasting blood ketone bodies as well as fat oxidation have been shown to be increased in patients with heart failure. The result is depletion of myocardial ATP, phosphocreatine and creatine kinase with decreased efficiency of mechanical work. A direct approach to manipulate cardiac energy metabolism consists in modifying substrate utilization by the failing heart. To date, the most effective metabolic treatments include several pharmacological agents that directly inhibit fatty acid oxidation. The results of current research are supporting the concept that shifting the energy substrate preference away from fatty acid metabolism and toward glucose metabolism could be an effective adjunctive treatment in patients with heart failure. Trimetazidine is the most studied drug in this context. Several small studies have evidenced the usefulness of such additional therapeutic tools for heart failure. More specifically, recent meta-analyses and a multicenter retrospective study have shown that additional use of trimetazidine in patients with heart failure, along with symptoms and cardiac function improvement, also provides a significant protective effect on all-cause mortality, cardiovascular events and hospitalization due to cardiac causes. Nevertheless, the exact role of metabolic therapy in heart failure is yet to be established, and a large multicenter randomized trial is necessary.