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1. Cardiovascular system Dr. Raya D. Marji, M.D Al-Balqa Applied University Faculty of Medicine

2. Infarct Modification by Reperfusion: Reperfusion is achieved by thrombolysis, angioplasty, or coronary arterial bypass graft. Late restoration of blood flow can incite greater local damage: so-called “reperfusion injury”.

3. Factors that contribute to reperfusion injury: Mitochondrial dysfunction : Ischemia causes swelling and rupture of the outer membrane, releasing mitochondrial contents>> promote apoptosis.  Myocyte hypercontractility : intracellular levels of calcium are increased. Uncontrolled contraction>>  cytoskeletal damage and cell death.  Free radicals , including superoxide anion (• − O2 ), hydrogen peroxide (H2O2), hypochlorous acid ( HOCl ), nitric oxide–derived  peroxynitrite , and hydroxyl radicals (•OH).  Leukocyte aggregation : occlude the microvasculature and contribute to the “no-reflow” phenomenon>> elaborate proteases and elastases.  5.    Platelet and complement activation also contribute to microvascular injury.

4. Microscopy: Contraction band necrosis (hypercontracted  sarcomeres are created by an influx of calcium across plasma membranes that heightens actin-myosin interactions ) In the absence of ATP, the sarcomeres cannot relax and get stuck in a tetanic state. 

5. Clinical Features: Severe, crushing substernal chest pain (or pressure) that can radiate to the neck, jaw, epigastrium, or left arm.  Pain typically lasts several minutes to hours. Not relieved by nitroglycerin or rest. Atypical signs (10% to 15%) or asymptomatic “silent” infarcts: common in patients with underlying diabetes mellitus and in older adults.

6. Rapid and weak pulse, diaphoretic (sweating) and nauseous patients. Dyspnea is common Massive MIs (involving more than 40% of the left ventricle):  cardiogenic shock develops.

7. Electrocardiographic abnormalities:  Q waves, ST segment changes, and T wave inversions.  Arrhythmias.

8. The laboratory evaluation: Based on measuring blood levels of macromolecules that leak out of injured myocardial cells through damaged cell membranes. These molecules include myoglobin , cardiac troponins T and I ( TnT , TnI ), creatine kinase (CK; specifically the myocardial isoform, CK-MB), and lactate dehydrogenase . Troponins (and to a lesser extent CK-MB) have high specificity and sensitivity for myocardial damage.

9. CK-MB:  Total CK activity is not a reliable marker of cardiac injury since various isoforms of CK are found in non-cardiac tissues.    CK-MB isoform —principally derived from myocardium, but also present at low levels in skeletal muscle—is a more specific indicator of heart damage.    CK-MB activity begins to rise within 2 to 4 hours of MI, peaks at 24 to 48 hours, and returns to normal within approximately 72 hours. 

10. Troponins:  TnI  and  TnT  normally are not found in the circulation. Detectable within 2 to 4 hours, with levels peaking at 48 hours and remaining elevated for 7 to 10 days.  Persistence of elevated troponin levels allows the diagnosis of an acute MI to be made long after CK-MB levels have returned to normal. With reperfusion, both troponin and CK-MB levels may peak earlier owing to more rapid washout of the enzyme from the necrotic tissue.

11. Consequences and Complications of Myocardial Infarction The overall in-hospital death rate for MI is approximately 7% to 8%.  MI associated with ST segment elevations experiencing higher mortality rates than those without.  Out-of-hospital mortality is poorer: one third of individuals with STEMIs die, usually of an arrhythmia within 1 hour of symptom onset.

12. Complications of Myocardial Infarction:

13. The risk for complications and the overall prognosis depends on infarct size, site, and type.  Large transmural infarcts: Cardiogenic shock, arrhythmias, and late CHF.  Anterior transmural MIs: Free wall rupture, expansion, aneurysm formation, and formation of mural thrombi. Posterior transmural infarcts: conduction blocks, right ventricular involvement, or both . Anterior infarcts have a much more guarded prognosis than those with posterior infarcts.

14. Ventricular remodeling   Noninfarcted regions undergo hypertrophy and dilation, in combination with the scarring and thinning of the infarcted zones .  The overall mortality rate within the first year is about 30%, including deaths occurring before the patient reaches the hospital. The annual mortality rate for patients who have suffered an MI is 3% to 4%.

15. Chronic Ischemic Heart Disease Ischemic cardiomyopathy. Progressive heart failure secondary to ischemic myocardial damage. Chronic IHD appears when the compensatory mechanisms (e.g., hypertrophy) of residual myocardium begin to fail.  Severe CAD can cause diffuse myocardial dysfunction, and even micro-infarction and replacement fibrosis, without any clinically evident episode of frank infarction.  The heart failure of chronic IHD is typically severe and is occasionally has new episodes of angina or infarction. 

16. HYPERTENSIVE HEART DISEASE A consequence of the increased demands placed on the heart by hypertension. Causes pressure overload and ventricular hypertrophy.  Myocyte hypertrophy is an adaptive response to pressure overload; persistent hypertension eventually can culminate in dysfunction, cardiac dilation, CHF, and even sudden death.

17. Hypertensive Heart disease: Left-sided hypertensive changes, secondary to systemic hypertension. Right-sided hypertensive changes—so-called “ cor  pulmonale.” Pulmonary hypertension.

18. Systemic (Left-Sided) Hypertensive Heart Disease The criteria for the diagnosis of systemic hypertensive heart disease:  (1) Left ventricular hypertrophy in the absence of other cardiovascular pathology (e.g., valvular stenosis). (2) History or pathologic evidence of hypertension.

19. MORPHOLOGY Left ventricular hypertrophy, typically without ventricular dilation until very late in the process. The heart weight can exceed 500 g (normal for a 60- to 70-kg individual is 320 to 360 g), and the left ventricular wall thickness can exceed 2.0 cm (normal is 1.2 to 1.4 cm). Left ventricular wall thickness imparts a stiffness that impairs diastolic filling and can result in left atrial dilation. In long-standing systemic hypertensive heart disease leading to congestive failure, the hypertrophic left ventricle typically is dilated. Microscopically, the transverse diameter of myocytes is increased and there is prominent nuclear enlargement and hyperchromasia (“boxcar nuclei”), as well as intercellular fibrosis.

20. In long-standing systemic hypertensive heart disease leading to congestive failure, the hypertrophic left ventricle typically is dilated.  Microscopically, the transverse diameter of myocytes is increased and there is prominent nuclear enlargement and  hyperchromasia  (“boxcar nuclei”), as well as intercellular fibrosis.

21. Systemic (left-sided) hypertensive heart disease Concentric thickening of the left ventricular wall causing reduction in lumen size.  Left atrial dilation (asterisk) due to stiffening of the left ventricle and impaired diastolic relaxation, leading to atrial volume overload.

22. Left ventricular hypertrophy

23. Clinical Features Compensated HHD: asymptomatic or:  1- Elevated blood pressure on routine physical examination. 2- ECG or echocardiographic findings of left ventricular hypertrophy. 3- Onset of atrial fibrillation (secondary to left atrial enlargement) and/or CHF. 

24. Prognosis: Depending on the severity and duration of the condition, the underlying cause of hypertension, and the adequacy of therapeutic control, patients can: (1) Enjoy normal longevity and die of unrelated causes. (2) Develop IHD. (3) Suffer renal damage or cerebrovascular stroke.  (4) Experience congestive heart failure.

25. Pulmonary Hypertensive Heart Disease— Cor Pulmonale Right ventricular hypertrophy and dilation—frequently accompanied by right-sided heart failure—caused by pulmonary hypertension attributable to primary disorders of the lung parenchyma or pulmonary vasculature.  Right ventricular dilation and hypertrophy caused by left ventricular failure (or by congenital heart disease) is substantially more common but is excluded by this definition. Cor pulmonale can be acute in onset or can have a slow and insidious onset.

26. MORPHOLOGY In acute cor pulmonale: right ventricular dilation. ** if an embolism causes sudden death, the heart may even be of normal size.  Chronic cor pulmonale: right ventricular (and often right atrial) hypertrophy. ** In extreme cases, the thickness of the right ventricular wall may be comparable to or even exceed that of the left ventricle.

27. Chronic cor pulmonale: The right ventricle is markedly dilated and hypertrophied. Thickened free wall and hypertrophied trabeculae. The shape and volume of the left ventricle have been distorted by the enlarged right ventricle.