What is the comprehensive approach to the management of ischemic heart disease, including its incidence, risk factors, clinical manifestations, spectrum, diagnostic tests, latest treatments, and prognosis?

Comprehensive Approach to Ischemic Heart Disease: A Lecture Guide for Medical Students

Ischemic heart disease (IHD) remains the leading cause of death and disability worldwide, affecting approximately 254.3 million people globally with 9 million deaths annually, requiring a systematic approach to diagnosis and management based on the latest guidelines. 1

Epidemiology and Global Burden

• IHD affects approximately 1.72% of the world's population (126 million individuals), with a prevalence rate of 1,655 per 100,000 population, projected to exceed 1,845 per 100,000 by 2030 2
• Men are more commonly affected than women, with incidence typically starting in the fourth decade and increasing with age 2
• In the United States, approximately 1 in 3 adults has some form of cardiovascular disease, including more than 13 million with coronary artery disease and more than 9 million with angina pectoris 3
• The economic burden is substantial, with direct and indirect costs reaching $156 billion in the US in 2008 3
• Despite declining global age-standardized death rates (-31.6% from 1990 to 2021), IHD remains the leading cause of mortality worldwide 1

Risk Factors

• Modifiable risk factors:

  • High systolic blood pressure and high LDL cholesterol are the factors contributing most to deaths and DALYs due to IHD 1
  • Smoking, hypertension, dyslipidemia, obesity, metabolic syndrome, and sedentary lifestyle 3
  • Diabetes mellitus significantly increases risk 3

• Non-modifiable risk factors:

  • Age (strongest determinant of survival) 3
  • Family history of premature CAD (onset in father/brother/son before 55 years or mother/sister/daughter before 65 years) 3
  • Male sex 3

• Other important prognostic factors:

  • Lower socioeconomic status 3
  • Coexisting conditions: chronic kidney disease, chronic pulmonary disease, malignancy 3
  • Cardiovascular comorbidities: heart failure, peripheral arterial disease, cerebrovascular disease 3
  • Psychosocial factors: depression, anxiety, poor social support 3

Clinical Manifestations and Spectrum

Angina Pectoris

• Typical angina characterized by:

  • Substernal chest discomfort described as "squeezing," "grip-like," "suffocating," or "heavy" 3
  • Radiation to neck, jaw, epigastrium, or arms 3
  • Precipitated by exertion or emotional stress 3
  • Relieved by rest or nitroglycerin within minutes 3

• Atypical presentations more common in:

  • Women (65% of women with ischemia in the WISE study presented with atypical symptoms) 3
  • Elderly patients 3
  • May include nausea, vomiting, midepigastric discomfort, or sharp chest pain 3

Clinical Spectrum of IHD

• Stable ischemic heart disease (SIHD): Predictable angina with consistent pattern 3
• Unstable angina (UA): New onset, increasing in frequency/intensity/duration, or occurring at rest 3
• Acute myocardial infarction (AMI): STEMI or NSTEMI 3
• Ischemic cardiomyopathy: Heart failure resulting from IHD 1
• Silent ischemia: Asymptomatic myocardial ischemia detected on diagnostic testing 3

Diagnostic Approach

Initial Evaluation

• History taking should focus on:

  • Characterization of chest pain (location, quality, duration, radiation, precipitating/alleviating factors) 3
  • Risk factor assessment 3
  • Classification of symptoms as typical, atypical, or noncardiac 3

• Physical examination may be normal in stable angina but should assess for:

  • Signs of heart failure 3
  • Valvular heart disease 3
  • Hypertrophic cardiomyopathy 3

Diagnostic Testing Algorithm

• Resting 12-lead ECG should be performed in all patients with suspected IHD 3

• Risk stratification to determine appropriate diagnostic pathway:

  • High-risk features: Refer for urgent evaluation (symptoms/findings suggesting high-risk lesions, prior sudden death/serious ventricular arrhythmia, prior stent in unprotected left main coronary artery) 3
  • Low-risk features: Outpatient evaluation appropriate 3

• Noninvasive testing based on pretest probability:

  • Exercise ECG testing: First-line test for patients with intermediate pretest probability who can exercise and have normal resting ECG 3
  • Stress imaging tests (recommended when exercise ECG is not possible or inconclusive):
    • Stress echocardiography 3
    • Myocardial perfusion imaging (nuclear) 3
    • Cardiac magnetic resonance (CMR) 3
  • Coronary CT angiography (CCTA): Reasonable for patients with intermediate probability of IHD 3
  • Coronary calcium scoring: CAC score ≥400 Agatston units indicates high risk 3

• Invasive coronary angiography: Indicated for high-risk patients or when noninvasive testing suggests high-risk coronary lesions 3

Risk Stratification

High Risk (>3% annual death or MI)

• Severe resting LV dysfunction (LVEF <35%) 3
• High-risk treadmill score (≤-11) 3
• Severe exercise LV dysfunction (peak exercise LVEF <45% or drop in LVEF with stress ≥10%) 3
• Stress-induced perfusion abnormalities affecting >10% myocardium 3
• Stress-induced LV dilation or wall motion abnormalities in multiple segments 3
• CAC score >400 Agatston units 3
• Multivessel obstructive CAD (≥70% stenosis) or left main stenosis (≥50%) on CCTA 3

Intermediate Risk (1-3% annual death or MI)

• Mild/moderate resting LV dysfunction (LVEF 35-49%) 3
• Intermediate-risk treadmill score (-11 to 5) 3
• Stress-induced perfusion abnormalities affecting 5-10% myocardium 3
• CAC score 100-399 Agatston units 3
• One vessel CAD with ≥70% stenosis or moderate CAD (50-69% stenosis) in 2 arteries on CCTA 3

Low Risk (<1% annual death or MI)

• Low-risk treadmill score (≥5) 3
• Normal or small myocardial perfusion defect at rest or stress affecting <5% myocardium 3
• Normal stress wall motion 3
• CAC score <100 Agatston units 3
• No coronary stenosis ≥50% on CCTA 3

Treatment Strategies

Goals of Treatment

• Reduce premature cardiovascular death 3
• Prevent complications (MI, heart failure) 3
• Maintain or restore functional capacity and quality of life 3
• Eliminate or minimize ischemic symptoms 3
• Minimize healthcare costs 3

Guideline-Directed Medical Therapy (GDMT)

• Antiplatelet therapy:

  • Aspirin (75-162 mg daily) for all patients with SIHD 3
  • Consider P2Y12 inhibitors for high-risk patients or those intolerant to aspirin 3

• Lipid-lowering therapy:

  • High-intensity statins for secondary prevention 3
  • Target LDL-C reduction >50% from baseline 3

• Anti-ischemic medications:

  • Beta-blockers (first-line for symptom relief and post-MI patients) 3
  • Calcium channel blockers (alternative for patients intolerant to beta-blockers) 3
  • Nitrates (short-acting for acute relief, long-acting for prophylaxis) 3

• Risk factor modification:

  • Blood pressure control (target <130/80 mmHg) 3
  • Diabetes management 3
  • Smoking cessation 3
  • Weight management and physical activity 3

Revascularization Strategies

• Indications for revascularization:

  • To improve survival in specific anatomic patterns (left main disease, multivessel disease, especially with reduced EF) 3
  • To improve symptoms when GDMT fails 3

• Percutaneous Coronary Intervention (PCI):

  • Preferred for single-vessel or less complex multivessel disease 3
  • Drug-eluting stents preferred over bare-metal stents 4
  • Requires dual antiplatelet therapy post-procedure 4

• Coronary Artery Bypass Grafting (CABG):

  • Preferred for complex multivessel disease, left main disease, and diabetic patients 3
  • Superior outcomes compared to PCI in patients with high SYNTAX scores (>32) 3

• Decision-making for revascularization:

  • Should involve a Heart Team approach (cardiologists, cardiac surgeons) 3
  • Consider patient preferences, comorbidities, and local expertise 3
  • Shared decision-making is essential, with clear explanation of risks, benefits, and costs 3

Emerging Therapies and Future Directions

• Metabolic therapy: Enhancing cardiac energy metabolism efficiency by optimizing the balance between fatty acid and carbohydrate oxidation 5

• Biopharmaceutical-based therapies:

  • Recombinant protein therapy 4
  • Gene therapy targeting angiogenesis 4
  • Cell transplantation to improve collateral blood flow 4

• Stem cell-based therapy: Emerging as a potential therapeutic option for myocardial regeneration 6

• ISCHEMIA trial findings: Routine invasive strategy did not reduce rates of death or MI compared to optimal medical therapy alone in patients with moderate-to-severe ischemia 3

Prognosis

• Prognosis varies based on:

  • Extent and severity of coronary disease 3
  • Left ventricular function 3
  • Presence of comorbidities 3
  • Response to medical therapy 3
  • Revascularization status 3

• Risk assessment tools:

  • Clinical parameters (age, sex, symptoms, risk factors) 3
  • Exercise test results 3
  • Imaging findings 3
  • Angiographic data 3

Clinical Pearls and Pitfalls

• Pearls:

  • Health status (symptoms, functional capacity, quality of life) strongly predicts survival and future ACS events 3
  • Frequency of angina is a strong predictor of subsequent ACS hospitalizations 3
  • Shared decision-making improves quality of care and patient satisfaction 3

• Pitfalls:

  • Overlooking atypical presentations in women and elderly patients 3
  • Failing to consider non-cardiac causes of chest pain 3
  • Overreliance on diagnostic tests without clinical correlation 3
  • Neglecting optimal medical therapy before or after revascularization 3
  • Not addressing psychosocial factors that affect prognosis 3