Determinanti del consumo di O2
Flusso a riposo
Flusso coronarico totale (ml/m’)
0 100 200300
25 50 75 100125150
Pressione arteriosa (mm Hg)
Flusso x 100 g di
Flusso x 100 g di
Flusso a riposo
Flusso coronarico totale (ml/m’)
0 100 200300
50 75 100125150175200
Pressione arteriosa (mm Hg)
Endotelio: un organo con 2 funzioni
Azione Antiadesione piastrinica
Adesione Proadesione piastrinica
Fattore VIII di Von Willebrand
Fattori di derivazione endoteliale
Fattori di rilasciamento endotelio-derivati: EDRF
Fattori di contrazione endotelio-derivati: EDCF
Patologia della liberazione di EDRF
Vanhoutte P, Boulanger MC: “L’endotelio: un ruolo fondamentale nella fisiopatologia cardiovascolare” 1994
L’Endotelio e il tono vascolare
1980: Furchgott e Zawadski scoprono che l’endotelio è essenziale per la vasodilatazione dell’acetilcolina
1986: il gruppo di Ignarro e quello di Moncada identificano nel NO (ossido di azoto) il fattore vasodilatante endotelio-dipendente
Transmural Distribution of Myocardial Blood Flow
Cross-section of the left ventricular wall in diastole and systole. Factors involved in the susceptibility of the subendocardium to the development of ischemia include the greater dependence of this region on diastolic perfusion and the greater degree of shortening, and therefore of energy expenditure, of this region during systole.
Epicardial coronary stenoses are associated with reductions in the subendocardial to subepicardial flow ratio.
Severe pressure-induced left ventricular hypertrophy, as well as heart failure with elevated left ventricular end-diastolic pressure, may also reduce the endocardial-to-epicardial flow ratio. When the markedly elevated left ventricular end-diastolic pressure in heart failure is corrected, subendocardial coronary flow reserve is restored and the endocardial-to-epicardial flow ratio is normalized.
Reduction of myocardial oxygen demand, for example by beta blockers, also decreases epicardial blood flow and increases perfusion pressure and thereby flow to the ischemic subendocardial region.
Energy losses across a stenosis. The pressure gradient due to friction losses within the stenosis (DP) is directly proportional to blood flow (Q), whereas separation losses at the exit to the stenosis due to formation of eddies increase with blood flow squared (Q2). Separation losses predominate at high blood flows.
Relation between pressure reduction across a stenosis (DP) and flow through the stenosis (Q)
Relationship between resting (dashed line) and maximal coronary blood flow (solid line) and percentage of diameter stenosis
Coronaria sinistra OAdx
ADENOSINA i.c 0.84
Schematic diagram of stunned myocardium
During coronary occlusion, a wall motion abnormality of the left ventricle is present in the region supplied by the occluded artery. With relief of ischemia and reestablishment of coronary blood flow, there is a persistent wall motion abnormality despite reperfusion and viable myocytes. There is then gradual improvement in function that requires hours to days for recovery.
Two possible additive components of postischemic dysfunction: (1) reperfusion-induced pathology, which can be restored through the use of a therapeutic intervention such as an antioxidant or calcium-limiting agent given transiently at the time of reperfusion; and (2) ischemic pathology from which the heart is slowly recovering. These may be additive to each other and to any additional reperfusion-induced component that is not amenable to the chosen intervention.
LE DIVERSE SEDI DEL DOLORE TORACICO
1: posizione del cuore nel torace
2: angina di petto
3: irradiazione nell’attacco card.
4: sede correlata ad emozioni e stati ansiosi
Da: M Caccavale. Inervista sul cuore e dintorni, 1984. Adn Kronos, Roma
ALCUNE POSSIBILI SEDI
ED IRRADIAZIONI DEL
DOLORE TORACICO DI
Sleisenger MH, Fordtran JS: Trattato di gastroenterologia, Piccin Ed, Padova
da: S Dalla Volta. La cardiopatia ischemica: dalla teoria alla clinica
agcon:cappio, capestro, laccio
kardia:cuore, bocca dello stomaco
Liddel Scott. Le Monnier
angor:stringimento, angoscia, pena
Castiglioni Mariotti. Loescher
heart burn:bruciore di stomaco
cardias:sbocco dell’esofago nello stomaco
angere: affliggere, angosciare
DOLORE TORACICO DI TIPO ANGINOSO ED ATTRIBUZIONE DELLA SINTOMATOLOGIA ALL’ESOFAGO
Pazienti% origine esofagea
Delmonico et al., 1968 11710
Brand et al., 1977 4346
Dart et al., 1980 9817
Ferguson et al., 1981 7218
Kline et al., 1981 1631
De Meester et al., 1982 5046
Katz et al., 1989 1631
Schofield et al., 1989 5248
Nevens et al., 1991 3750
Voskuil et al., 1996 2836
Frøbert et al., 1996 4625
Chauhan et al., 1996 3266
Fass et al., 1998 3762
Ho et al., 1998 8046
Börjesson et al., 1998 2035
Romand et al., 1999 4344
Netzer et al., 1999 30354
Differential diagnosis of chest pain according to location where pain starts. Serious intrathoracic or subdiaphragmatic diseases are usually associated with pains that begin in the left anterior chest, left shoulder, or upper arm, the interscapular region, or the epigastrium. The scheme is not all inclusive (e.g., intercostal neuralgia occurs in locations other than the left, lower anterior chest area).
Factors influencing the balance between myocardial O2 requirements (left) and supply (right). Arrows indicate effects of nitrates. In relieving angina pectoris, nitrates exert favorable effects by reducing O2 requirements and increasing supply. Although a reflex increase in heart rate would tend to reduce the time for coronary flow, dilation of collaterals and enhancement of the pressure gradient for flow to occur as the left ventricular end-diastolic pressure (LVEDP) falls tend to increase coronary flow. AoP = aortic pressure; NC = no change. (From Frishman WH: Pharmacology of the nitrates in angina pectoris. Am J Cardiol 56:8I, 1985. By permission of Excerpta Medica.)
Elettrogenesi della “lesione”
Acute ischemia may alter ventricular action potentials by inducing lower resting membrane potential, decreased amplitude and velocity of phase 0, and an abbreviated action potential duration (pathological early repolarization). These electrophysiological effects create a voltage gradient between ischemic and normal cells during different phases of the cardiac electrical cycle. The resulting currents of injury are reflected on the surface electrocardiogram by deviation of the ST segment
Current-of-injury patterns with acute ischemia. With predominant subendocardial ischemia (A), the resultant ST vector is directed toward the inner layer of the affected ventricle and the ventricular cavity. Overlying leads therefore record ST depression. With ischemia involving the outer ventricular layer (B) (transmural or epicardial injury), the ST vector is directed outward. Overlying leads record ST elevation. Reciprocal ST depression can appear in contralateral leads.
Miocardioscintigrafia da sforzo (o da stress)
BMJ 1994;309:901-911 (8 October)
Mortality Risk Reduction Associated With Smoking Cessation in Patients
With Coronary Heart Disease. A Systematic Review
Julia A. Critchley, MSc, DPhil; Simon Capewell, MD, FRCPE JAMA. 2003;290:86-97.
Objective To conduct a systematic review to determine the magnitude of risk reduction achieved by smoking cessation in patients with CHD.
Data Sources Nine electronic databases were searched from start of database to April 2003, supplemented by cross-checking references, contact with experts, and with large international cohort studies (identified by the Prospective Studies Collaboration).
Study Selection Prospective cohort studies of patients who were diagnosed with CHD were included if they reported all-cause mortality and had at least 2 years of follow-up. Smoking status had to be measured after CHD diagnosis to ascertain quitting.
Data Extraction Two reviewers independently assessed studies to determine eligibility, quality assessment of studies, and results, and independently carried out data extraction using a prepiloted, standardized form.
Data Synthesis From the literature search, 665 publications were screened and 20 studies were included. Results showed a 36% reduction in crude relative risk (RR) of mortality for patients with CHD who quit compared with those who continued smoking (RR, 0.64; 95% confidence interval [CI], 0.58-0.71). Results from individual studies did not vary greatly despite many differences in patient characteristics, such as age, sex, type of CHD, and the years in which studies took place. Adjusted risk estimates did not differ substantially from crude estimates. Many studies did not adequately address quality issues, such as control of confounding, and misclassification of smoking status. However, restriction to 6 higher-quality studies had little effect on the estimate (RR, 0.71; 95% CI, 0.65-0.77). Few studies included large numbers of elderly persons, women, ethnic minorities, or patients from developing countries.
Conclusions Quitting smoking is associated with a substantial reduction in risk of all-cause mortality among patients with CHD. This risk reduction appears to be consistent regardless of age, sex, index cardiac event, country, and year of study commencement.
Effects of nitrates in generating NO+ and stimulating guanylate cyclase to cause vasodilation. Note the role of cysteine cascade in stimulating guanylate cyclase. Previously, sulfhydryl (SH) depletion was thought to explain nitrate tolerance. Current emphasis is on the generation of peroxynitrite, which in turn inhibits the conversion of guanosine triphosphate (GTP) to cyclic guanosine monophosphate (GMP). Note that mononitrates bypass hepatic metabolism.
The mechanisms of action of the nitrates are complex. These drugs decrease cardiac demand and may increase coronary blood supply through a variety of actions. It is likely that the various mechanisms that act to provide relief to angina patients or prevent myocardial ischemia differ among individuals. LV = left ventricular; RV = right ventricular.
Effects of beta blockade on the ischemic heart. Beta blockade has a beneficial effect on ischemic myocardium unless (1) the preload rises substantially as in left-sided heart failure or (2) vasospastic angina is present, in which case spasm may be promoted in some patients. Note the recent proposal that beta blockade diminishes exercise-induced vasoconstriction.
Graphs showing survival for medically treated CASS patients. A, Patients with one-, two-, or three-vessel disease and an ejection fraction of 50 to 100 percent stratified by the number of diseased vessels (DISVES). B, Patients with one-, two-, or three-vessel disease and an ejection fraction of 35 to 49 percent stratified by the number of diseased vessels. C, Patients with one-, two-, or three-vessel disease and an ejection fraction of 0 to 34 percent stratified by the number of diseased vessels.
Adjusted hazard (mortality) ratios comparing coronary artery bypass grafting (CABG) and medical therapy for nine coronary anatomy severity groups (GR) according to the number of vessels diseased (VD), the presence or absence of a 95 percent proximal stenosis (95 percent), and involvement of the left anterior descending coronary artery (LAD). B, Adjusted hazard (mortality) ratios comparing CABG and percutaneous transluminal angioplasty (PTCA) for nine coronary anatomy groups according to the number of vessels diseased, the presence or absence of a 95 percent proximal stenosis, and LAD involvement.
Two-year cumulative mortality rates for three treatment strategies. Significant differences were seen between revascularization and angina-guided strategies (P<.005) and between revascularization and ischemia-guided strategies (P<.05). Angina-guided and ischemia-guided strategies were not significantly different from each other (P=.34). Asymptomatic Cardiac Ischemia Pilot (ACIP) Study Two-Year Follow-up : Outcomes of Patients Randomized to Initial Strategies of Medical Therapy Versus Revascularization. Circulation, Apr 1997; 95: 2037 - 2043.
Schematic representation of the causes of unstable angina. Each of the five bars represents one of the etiologic mechanisms, and the red portion of the bar represents the extent to which the mechanism is operative. A, Most common form of unstable angina in which atherosclerotic plaque causes moderate (60 percent diameter) obstruction and acute thrombus overlying plaque causes very severe (90 percent diameter) narrowing. B, Mild coronary obstruction, adjacent to which there is intense (90 percent diameter) vasoconstriction.
Platelets initiate thrombosis at the site of a ruptured plaque: the first step is platelet adhesion (1) via the glycoprotein Ib receptor in conjunction with von Willebrand factor. This is followed by platelet activation (2), which leads to a shape change in the platelet, de-granulation of the alpha and
dense granules, and expression of glycoprotein IIb/IIIa receptors on the platelet surface with activation of the receptor, such that it can bind fibrinogen. The final step is platelet aggregation (3), in which fibrinogen (or von Willebrand factor) binds to the activated glycoprotein IIb/IIIa receptors of two platelets. Aspirin (ASA) and clopidogrel act to decrease platelet activation, whereas the glycoprotein IIb/IIIa inhibitors inhibit the final step of platelet aggregation.
Stratificazione del rischio
nelle sindromi coronariche acute
Pooled data from CAPTURE, PRISM-PLUS, and PURSUIT trials of unstable angina, showing benefit of glycoprotein IIb/IIIa inhibition during medical therapy only (left panel), during, and immediately after percutaneous coronary intervention (PCI, right panel).
Diagnosi di dimissioni ospedaliere nel triennio 1996 - 1998
IMA = infarto miocardico acuto; AP = angina pectoris
+ Direct PTCA, statine
Bypass, PTCA, TL, ACE-I
Schematic representation of the progression of myocardial necrosis after coronary artery occlusion. Necrosis begins in a small zone of the myocardium beneath the endocardial surface in the center of the ischemic zone. This entire region of myocardium (dashed outline) depends on the occluded vessel for perfusion and is the area at risk. Note that a very narrow zone of myocardium immediately beneath the endocardium is spared from necrosis because it can be oxygenated by diffusion from the ventricle.
Temporal sequence of early biochemical, ultrastructural, histochemical, and histological findings after onset of MI. At the top of the figure are schematically shown the time frames for early and late reperfusion of the myocardium supplied by an occluded coronary artery. For approximately one-half hour after the onset of even the most severe ischemia, myocardial injury is potentially reversible; after that there is progressive loss of viability that is complete by 6 to 12 hours. The benefits of reperfusion (both early and late) are greatest when it is achieved early, with progressively smaller benefits occurring as reperfusion is delayed.
P = 0,5
Objective documentation of the circadian pattern in the onset of myocardial infarction (MI).
Hyperacute phase of extensive anterior-lateral myocardial infarction. Marked ST elevation melding with prominent T waves is present across the precordium, as well as in leads I and aVl. ST depression, consistent with a reciprocal change, is seen in leads III and aVf. Q waves are present in leads V3 through V6. Marked ST elevations with tall T waves caused by severe ischemia are sometimes referred to as a monophasic current-of-injury pattern. A paradoxical increase in R wave amplitude (V2 and V3 ) may accompany this pattern. This tracing also shows left axis deviation with small or absent inferior R waves, which raises the possibility of a prior inferior infarct.
Sequence of depolarization and repolarization changes with (A) acute anterior-lateral and (B) acute inferior wall Q wave infarctions. With anterior-lateral infarcts, ST elevation in leads I, aVl, and the precordial leads may be accompanied by reciprocal ST depression in leads II, III, and aVf. Conversely, acute inferior (or posterior) infarcts may be associated with reciprocal ST depression in leads V1 to V3.
Variability of electrocardiogram (ECG) patterns with acute myocardial ischemia. The ECG may also be normal or nonspecifically abnormal. Furthermore, these categorizations are not mutually exclusive. For example, a non-Q-wave infarct can evolve into a Q wave infarct, ST elevation can be followed by a non-Q-wave infarct, or ST depression and T wave inversion can be followed by a Q wave infarct.
Plot of the appearance of cardiac markers in blood versus time after onset of symptoms. Peak A, early release of myoglobin or CK-MB isoforms after AMI; peak B, cardiac troponin after AMI; peak C, CK-MB after AMI; peak D, cardiac troponin after unstable angina. Data are plotted on a relative scale, where 1.0 is set at the AMI cutoff concentration
Relationship between coronary blood flow and mortality in AMI
Adapted from Tiefenbrunn AJ, Sobel BE. Circulation. 1992;85:2311-2315.
TIMI Risk Score for STEMI for predicting 30-day mortality. STE = ST elevation; LBBB = left bundle branch block; h/o = history of; HTN = hypertension.
Impact of left ventricular function on survival after myocardial infarction. The curvilinear relationship between left ventricular ejection fraction (LVEF) for patients treated in the thrombolytic era is shown.