Cardiopatia ischemica cronica: I clinical trials che mettono a confronto PCI vs terapia medica rispondono alla giusta domanda?

Background: Spesso nei Clinical Trials I termini “Malattia coronarica aterosclerotica e cardiopatia ischemica” sono utilizzati indifferentemente. Questo puo’ creare confusion soprattutto nella scelta dei criteri di inclusion e di esclusione dei trial Clinici e percio’ portare a risultati incerti. Scopo dello studio: Il nostro obiettivo e’ investigare se la popolazione arruolata ne trial clinici ischemici che confrontano terapia medica con rivascolarizzazione percutanea riflette pazienti con ischemia dimostrata ad un precedente test non invasivo e quanti pazienti sono inclusi nei trial con la sola evidenza di malattia aterosclerotica (senza ischemia). Metodi: I trial dai quali sono stati ottenuti (numero di pazienti scrinati, numero di pazienti arruolati, numero di pazienti con test da sfozo positivo o senza stress test) sono: ACME I, ACME II, RITA I, RITA II, MASS I, MASS II, AVERT, ACIP and COURAGE. I risultati pubblicati sono stati utilizzati per calcolare il numero dei pazienti inclusi nei trial con test provocativo negativo, ma con malattia coronarica rilevante ed il numero dei pzienti esclusi dai trial con test da sforzo positivo o angina (ma senza stenosi coronarica significativa al momento dell’angiografia). Risultati: Un totale di 195.213 pazienti sono stati screenati fra il 1998 ed il 2011. Circa un 30% di pazienti sono stati esclusi se non incontravano i criteri angiografici anche se era presente ischemia al test provocativo; circa il 20% dei pazienti per trial venivano inclusi senza ischemia dimostrabile. Conclusioni: I trial clinici hanno contribuito alla confusione fra malattia aterosclerotica e cardiopatia ischemica. Cio’ puo’ essere un fattore limitante per interpretazione dei risultati e per la loro applicazione nella pratica clinica

Myocardial protection during PCI in STEMI : strategy reperfusion effects in acute MI patients (stream study)

Background: Numerous strategies have been proposed to preserve cardiac muscle during myocardial infarction. Intracoronary adenosine and post conditioning has been reported to reduce infarct size in patients with acute MI. Our purpose is to compare these two strategies. Methods: Consecutive patients undergoing primary percutaneous coronary intervention (PCI) for STEMI within 6 hours after symptom onset were randomly assigned to the postconditioning, adenosine or controls group. Exclusion criteria were: previous MI, revascularization, controindication to PCI or cardiogenic shock. Adenosine was administrated in 2 mg bolus with over the wire cathether; postconditioning included 4 sequencies of 1 minute balloon inflation/one minute reperfusion. Primary end point include: wall motion score index (1-6 months), ST resolution 30 minute after the procedure, cardiac markers (peak values) and infarct related end diastolic wall tickness. 2-way ANOVA is used to identify interaction between the treatment modality. A P<0.05 will be considered statistically significant. Results: 46 patients were enrolled. The 3 groups were similar for age, sex, and infarct location. There was no difference between adenosine administration and postconditioning in terms of primary endpoint. There were statistical significative results among treatments (adenosine +postconditioning) vs controls. Wall motion score index at 6 months was improved in treated patients (adenosine group 1.15 WMSI mean, postconditioning group 1.15, controls group 1.89- p<0.05) Treated patients showed reduction in wall tickness (calculate as the percentage reduction in tickness of the ischemic wall between discharge and six months follow up) (adenosine group 13.0%, postconditioning group 19.2%, controls group 5.1% p<0.05). Complete ST-segment resolution occurred in 56 % of patients in the adenosine group and in 68 % of patients in postconditioning group and 27% of patients in the conventional PCI group (P<0.05). Conclusion: Myocardial protection is feasible and well tolerated and adjunt to primary PCI ameliorat

Evidence of Myocardial Edema in Obstructive Tako-tsubo Cardiomyopathy Complicated by Cardiogenic Shock

the contemporary presence of left ventricular (LV) outflow tract obstruction, systolic anterior motion of the anterior mitral leaflet, and acute mitral regurgitation may occur in t ako-tsubo cardiomyopathy. Although myocardial edema has been reported in patients with tako-tsubo cardiomyopathy, to the best of our knowledge it has never been described in the setting of LV outflow obstruction and the presence of cardiogenic shock. We report the case of a 65-year-old woman who developed t ako-tsubo cardiomyopathy followed by acute cardiogenic shock. the echo-Doppler assessment revealed LV apical ballooning, moderate-to-severe mitral regurgitation, and an estimated peak systolic pressure gradient at LV outflow tract of 64 mmHg. the LV outflow obstruction and mitral regurgitation resolved shortly after the intravenous administration of atenolol (1.25 mg). the cardiogenic shock was completely resolved following the infusion of low-dose dobutamine: 2 γ/kg/min. In the following days, an echo-Doppler examination revealed a marked reduction in the thickness of the LV proximal hypertrophied septum (from 20 mm to 14 mm), while a cardiac magnetic resonance imaging study showed signs of mild edema of the mid-ventricular and apical septum

Safety profile of statins alone or combined with ezetimibe : a pooled analysis of 27 studies including over 22,000 patients treated for 6-24 weeks

Aims:  The aim of this analysis was to assess the overall safety and tolerability profiles of various statins + ezetimibe vs. statin monotherapy and to explore tolerability in sub-populations grouped by age, race, and sex. Methods:  Study-level data were combined from 27 double-blind, placebo-controlled or active-comparator trials that randomized adult hypercholesterolemic patients to statin or statin + ezetimibe for 6-24 weeks. In the full cohort, % patients with AEs within treatment groups (statin: N = 10,517; statin + ezetimibe: N = 11,714) was assessed by logistic regression with terms for first-/second-line therapy (first line = drug-naïve or rendered drug-naïve by washout at study entry; second line = ongoing statin at study entry or statin run-in), trial within first-/second-line therapy, and treatment. The same model was fitted for age (< 65, ≥ 65 years), sex, race (white, black, other) and first-/second-line subgroups with additional terms for subgroup and subgroup-by-treatment interaction. Results:  In the full cohort, the only significant difference between treatments was consecutive AST or ALT elevations ≥ 3 × upper limit of normal (ULN) (statin: 0.35%, statin + ezetimibe: 0.56%; p = 0.017). Significantly more subjects reported ≥ 1 AE; drug-related, hepatitis-related and gastrointestinal-related AEs; and CK elevations ≥ 10 × ULN (all p ≤ 0.008) in first-line vs. second-line therapy studies with both treatments. AEs were generally similar between treatments in subgroups, and similar rates of AEs were reported within age and race subgroups; however, women reported generally higher AE rates. Conclusions:  In conclusion, in second-line studies, ongoing statin treatment at study entry likely screened out participants for previous statin-related AEs and tolerability issues. These results describe the safety profiles of widely used lipid-lowering therapies and encourage their appropriate and judicious use in certain subpopulations

Interventional cardiology : Cost-effectiveness of PCI guided by fractional flow reserve

Coronary revascularization strategies have been evaluated in numerous clinical trials. As coronary revascularization has become more common, concerns over financial costs have increased

Circulating endothelial progenitor cells are actively involved in the reparative mechanisms of stable ischemic myocardium

Background: Myocardial fibrosis (MF) is an adverse correlate of severe aortic valve stenosis (SAVS). microRNA expression modulates different pathophysiological pathways in cardiovascular disease. In particular miRNA­21, has been associated to MF due to pressure overload. Non­invasive estimation of MF, using speckle­tracking echocardiography (2D­STE), could be useful in determining early myocardial damage. Purpose: To analyze the correlation between 2D­STE parameters, MF, plasmatic and tissue miRNA­21 in SAVS. Methods: We evaluated 36 consecutive patients (75.2±8 y.o., 63% F) with SAVS and preserved ejection fraction (EF), undergoing to surgical aortic valve replacement (AVR; Euroscore II 2.28±1.13%; Logistic Euroscore: 6±4.1%). Clinical, ECG, biohumoral evaluation (including plasma miRNA­21) and a complete echocardiography, including 2D­STE, was performed before AVR. 28 patients eventually underwent AVR and, in 23 of them, a basal interventricular septum biopsy was performed. MF and tissue miRNA­21 expression (micro­dissection) were evaluated in each sample. Results: All patients with SAVS (AVAi 0.33±0.1 cm2/m2; V max 4.4±0.4 m/sec; Mean Grad. 50±9 mmHg) showed concentric hypertrophy (LVMi 147±20.7 g/m2, RWT 0.51±0.07), diastolic dysfunction and increased Valvulo­Arterial Impedance (ZVA: 5.9±2.3 mmHg/ml/m2). Despite a preserved EF (66±11%), an altered global and septal deformation (Global longitudinal strain, GLS −13±6.1; Global longitudinal strain rate, GLSr −0.8±0.2 1/sec; Global early diastolic Sr, GLSrE 1±0.35 1/sec; Septal longitudinal strain, SLS −8.6±2.8%; SL­Sr −0,6±0.1 1/sec; SL­SrE 0.6±0.29 1/sec) were observed. We found a significant association between MF and 2D­STE parameters, stroke volume and end­diastolic pressure (all p&lt;0.05). Tissue miRNA­21 was mainly expressed in fibrous tissue than in myocardium (p&lt;0.0001). Myocardial miRNA­21 was associated with AVAi (r=0.46; p=0.043) and cardiac index (r=0.5; p=0.02) while fibrous tissue miRNA­21 was associated to GLS (r=0.8; p=0.0003), GLSrE (r=−0.72; p=0.005), SLS (r=0.6; p=0.01), SL­Sr (r=0.54; p=0.03), SL­SrE (r=0.5; p=0.04) and PAPs (r=0.66; p=0.004). Plasma miRNA­21 was associated to MF (r=0.5; p=0.02) and septal longitudinal strain (r=0.38; p=0.037). Conclusions: In SAVS with preserved EF, MF is associated to impaired myocardial deformation. miRNA­21 has a potential pathophysiological role in fibrogenesis. Non­invasive evaluation of plasmatic miRNA­21 and 2D­STE could be useful in risk stratification, to optimize the timing of surgery in SAVS patients

Myocardial infarction with nonobstructive coronary arteries: from pathophysiology to therapeutic strategies

: Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a heterogeneous group of clinical entities characterized by clinical evidence of acute myocardial infarction (AMI) with normal or near-normal coronary arteries on coronary angiography (stenosis &lt; 50%) and without an over the alternative diagnosis for the acute presentation. Its prevalence ranges from 6% to 11% among all patients with AMI, with a predominance of young, nonwhite females with fewer traditional risks than those with an obstructive coronary artery disease (MI-CAD). MINOCA can be due to either epicardial causes such as rupture or fissuring of unstable nonobstructive atherosclerotic plaque, coronary artery spasm, spontaneous coronary dissection and cardioembolism in-situ or microvascular causes. Besides, also type-2 AMI due to supply-demand mismatch and Takotsubo syndrome must be considered as a possible MINOCA cause. Because of the complex etiology and a limited amount of evidence, there is still some confusion around the management and treatment of these patients. Therefore, the key focus of this condition is to identify the underlying individual mechanisms to achieve patient-specific treatments. Clinical history, electrocardiogram, echocardiography, and coronary angiography represent the first-level diagnostic investigations, but coronary imaging with intravascular ultrasound and optical coherent tomography, coronary physiology testing, and cardiac magnetic resonance imaging offer additional information to understand the underlying cause of MINOCA. Although the prognosis is slightly better compared with MI-CAD patients, MINOCA is not always benign and depends on the etiopathology. This review analyzes all possible pathophysiological mechanisms that could lead to MINOCA and provides the most specific and appropriate therapeutic approach in each scenario

Perspectives in noninvasive imaging for chronic coronary syndromes

Both the latest European guidelines on chronic coronary syndromes and the American guidelines on chest pain have underlined the importance of noninvasive imaging to select patients to be referred to invasive angiography. Nevertheless, although coronary stenosis has long been considered the main determinant of inducible ischemia and symptoms, growing evidence has demonstrated the importance of other underlying mechanisms (e.g., vasospasm, microvascular disease, energetic inefficiency). The search for a pathophysiology-driven treatment of these patients has therefore emerged as an important objective of multimodality imaging, integrating "anatomical" and "functional" information. We here provide an up-to-date guide for the choice and the interpretation of the currently available noninvasive anatomical and/or functional tests, focusing on emerging techniques (e.g., coronary flow velocity reserve, stress-cardiac magnetic resonance, hybrid imaging, functional-coronary computed tomography angiography, etc.), which could provide deeper pathophysiological insights to refine diagnostic and therapeutic pathways in the next future

Multicentric Atrial Strain COmparison between Two Different Modalities: MASCOT HIT Study

Two methods are currently available for left atrial (LA) strain measurement by speckle tracking echocardiography, with two different reference timings for starting the analysis: QRS (QRS-LASr) and P wave (P-LASr). The aim of MASCOT HIT study was to define which of the two was more reproducible, more feasible, and less time consuming. In 26 expert centers, LA strain was analyzed by two different echocardiographers (young vs senior) in a blinded fashion. The study population included: healthy subjects, patients with arterial hypertension or aortic stenosis (LA pressure overload, group 2) and patients with mitral regurgitation or heart failure (LA volume–pressure overload, group 3). Difference between the inter-correlation coefficient (ICC) by the two echocardiographers using the two techniques, feasibility and analysis time of both methods were analyzed. A total of 938 subjects were included: 309 controls, 333 patients in group 2, and 296 patients in group 3. The ICC was comparable between QRS-LASr (0.93) and P-LASr (0.90). The young echocardiographers calculated QRS-LASr in 90% of cases, the expert ones in 95%. The feasibility of P-LASr was 85% by young echocardiographers and 88% by senior ones. QRS-LASr young median time was 110 s (interquartile range, IR, 78-149) vs senior 110 s (IR 78-155); for P-LASr, 120 s (IR 80-165) and 120 s (IR 90-161), respectively. LA strain was feasible in the majority of patients with similar reproducibility for both methods. QRS complex guaranteed a slightly higher feasibility and a lower time wasting compared to the use of P wave as the reference

Mortality Prediction of the CHA2DS2-VASc Score, the HAS-BLED Score, and Their Combination in Anticoagulated Patients with Atrial Fibrillation

Background and Objectives: Atrial fibrillation (AF) is associated with increased mortality, predictors of which are poorly characterized. We investigated the predictive power of the commonly used CHA2DS2-VASc score (congestive heart failure, hypertension, age &ge; 75 years [doubled], diabetes, stroke/transient ischemic attack/thromboembolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease, or aortic plaque], age 65&ndash;75 years, sex category [female]), the HAS-BLED score (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio [INR], elderly [age &ge; 65 years], drugs/alcohol concomitantly), and their combination for mortality in AF patients. Methods: The PREvention oF thromboembolic events&mdash;European Registry in Atrial Fibrillation (PREFER in AF) was a prospective registry including AF patients across seven European countries. We used logistic regression to analyze the relationship between the CHA2DS2-VASc and HAS-BLED scores and outcomes, including mortality, at one year. We evaluated the performance of logistic regression models by discrimination measures (C-index and DeLong test) and calibration measures (Hosmer and Lemeshow goodness-of-fit and integrated discrimination improvement (IDI), with bootstrap techniques for internal validation. Results: In 5209 AF patients with complete information on both scores, average one-year mortality was 3.1%. We found strong gradients between stroke/systemic embolic events (SSE), major bleeding and&mdash;specifically&mdash;mortality for both CHA2DS2-VASc and HAS-BLED scores, with a similar C-statistic for event prediction. The predictive power of the models with both scores combined, removing overlapping components, was significantly enhanced (p &lt; 0.01) compared to models including either CHA2DS2-VASc or HAS-BLED alone: for mortality, C-statistic: 0.740, compared to 0.707 for CHA2DS2-VASc or 0.646 for HAS-BLED alone. IDI analyses supported the significant improvement for the combined score model compared to separate score models for all outcomes. Conclusions: Both the CHA2DS2-VASc and the HAS-BLED scores predict mortality similarly in patients with AF, and a combination of their components increases prediction significantly. Such combination may be useful for investigational and&mdash;possibly&mdash;also clinical purposes