2.4 Valvular Heart Disease, Infective Endocarditis & Hypertension

Valvular Heart Disease: Auscultation & Hemodynamics

Valvular heart disease produces characteristic murmurs and hemodynamic alterations resulting from pressure overload (stenosis) or volume overload (regurgitation).

Aortic Stenosis (AS)

• Etiology: Calcific degeneration of a normal trileaflet valve (predominant in patients > 70 years); calcification of a congenital bicuspid aortic valve (presents earlier, aged 40-60 years); and rheumatic heart disease (associated with fused commissures and concomitant mitral valve involvement).
• Pathophysiology: Progressive narrowing of the aortic valve orifice restricts left ventricular outflow, producing concentric left ventricular hypertrophy (LVH) to normalize wall stress. Elevated intracardiac pressures lead to diastolic dysfunction, reduced coronary perfusion reserve, and eventual systolic failure.
• Clinical Presentation: The classic symptomatic triad spans Angina (average survival 5 years without intervention), Syncope on exertion (survival 3 years), and Dyspnea from heart failure (survival 2 years)—frequently remembered by the mnemonic SAD.
• Physical Examination:
  • Harsh, crescendo-decrescendo ejection systolic murmur, loudest at the right second intercostal space, radiating characteristically into both carotid arteries.
  • Pulsus parvus et tardus: Carotid pulse is slow-rising with diminished peak amplitude.
  • Soft, single, or absent second heart sound (A2 component attenuated or delayed, producing paradoxical splitting of S2).
  • Palpable systolic thrill over the base and sustained, non-displaced heaving apical impulse.
  • Gallavardin Phenomenon: Radiates musical, high-frequency components to the cardiac apex, occasionally mimicking mitral regurgitation.
• Management: Severe high-gradient AS typically has concordant findings: valve area <= 1.0 cm2, mean gradient >= 40 mmHg and peak velocity >= 4.0 m/s. Discordant measurements require integrated assessment of flow, measurement accuracy and valve calcification before classifying severity. Once symptoms supervene or LVEF drops < 50%, mechanical relief via Surgical Aortic Valve Replacement (SAVR) or Transcatheter Aortic Valve Implantation (TAVI) is mandatory. Medical therapy cannot halt mechanical progression, and vasodilators must be used with extreme caution to avoid sudden hypoperfusion.

Aortic Regurgitation (AR)

• Etiology: Valvular causes (infective endocarditis, bicuspid valve, rheumatic fever) and aortic root dilation (long-standing severe hypertension, Marfan syndrome, ascending aortic dissection, tertiary syphilis).
• Pathophysiology: Regurgitation of blood from the aorta back into the left ventricle during diastole causes combined volume and pressure overload, inducing massive left ventricular eccentric hypertrophy and chamber dilation ("cor bovinum").
• Physical Examination:
  • High-pitched, blowing, early diastolic decrescendo murmur heard best along the left sternal border (3rd/4th intercostal space) with the patient sitting forward, in full expiration.
  • Austin Flint Murmur: Mid-to-late diastolic low-pitched rumbling murmur at the apex, caused by the regurgitant jet striking the anterior mitral valve leaflet, causing functional mitral stenosis.
  • Marked widened pulse pressure (elevated systolic BP with severely decreased diastolic BP, e.g., 160/45 mmHg).
  • Peripheral hemodynamic signs: Corrigan / Water-hammer pulse (bounding pulse with rapid collapse); Quincke sign (capillary pulsations in the nail bed); de Musset sign (head nodding synchronous with pulse); Duroziez sign (systolic and diastolic murmurs over the femoral artery with gentle compression).
• Management: Asymptomatic severe AR is monitored with serial echocardiograms. Symptomatic patients or those with LVEF <= 50% or severe LV end-systolic dimension (> 50 mm) require surgical valve replacement.

Mitral Stenosis (MS)

• Etiology: Almost exclusively Rheumatic Heart Disease (RHD) resulting from prior untreated group A streptococcal pharyngitis. Remains a significant clinical burden in the Caribbean basin and developing regions, manifesting 15 to 30 years following acute rheumatic fever.
• Pathophysiology: Fibrous thickening, commissural fusion, and chordal shortening create a funnel-shaped "fish-mouth" mitral orifice. Restriction of left ventricular diastolic filling elevates left atrial pressure, causing progressive left atrial enlargement, pulmonary venous hypertension, reactive pulmonary arterial hypertension, and secondary right heart failure.
• Complications: Left atrial dilation predisposes to atrial fibrillation, atrial thrombus and systemic embolism. Risk depends on rhythm, atrial findings and prior embolism; it is not a single fixed annual percentage for all patients.
• Physical Examination:
  • Loud first heart sound (S1) caused by forceful closure of pliable leaflets.
  • Opening Snap (OS): High-pitched early diastolic sound occurring shortly after S2; a shorter A2-to-OS interval signifies higher left atrial pressure and more severe stenosis.
  • Low-pitched, rumbling mid-diastolic murmur with presystolic accentuation (presystolic accentuation disappears in atrial fibrillation), heard best at the apex using the bell of the stethoscope in the left lateral decubitus position.
  • Signs of pulmonary hypertension: Loud P2, parasternal heave (RV hypertrophy), and elevated JVP with prominent V waves.
• Management: Use warfarin (INR 2–3) for rheumatic MS with AF, previous systemic embolism or left atrial thrombus; do not substitute a DOAC in moderate-to-severe rheumatic MS. Control heart rate with beta-blockers. For significant symptomatic stenosis, consider Percutaneous Mitral Balloon Commissurotomy (PMBC) when anatomy is favorable, no atrial thrombus is present and MR is no more than mild; otherwise consider surgery.

Mitral Regurgitation (MR)

• Etiology: Primary/organic (mitral valve prolapse, infective endocarditis, ruptured chordae tendineae, rheumatic disease) or secondary/functional (ischemic cardiomyopathy, LV dilation with papillary muscle displacement).
• Physical Examination: Blowing holosystolic (pansystolic) murmur at the cardiac apex radiating widely into the left axilla; diminished S1; laterally displaced hyperdynamic apical impulse; and S3 gallop reflecting rapid volume overload during early diastolic filling.

Infective Endocarditis: Modified Duke Criteria & Regimens

Infective endocarditis (IE) is an invasive microbial infection of the endocardial surface of the heart, most commonly affecting the heart valves.

Pathophysiological Sequence

1. Endothelial disruption secondary to turbulent flow or intracardiac foreign material.
2. Platelet and fibrin adherence, forming sterile Non-Bacterial Thrombotic Endocarditis (NBTE).
3. Transient bacteremia allowing circulating microbes to colonize the sterile thrombus.
4. Bacterial proliferation and maturation into an infected, friable vegetation, shielded from host phagocytes by an overlying fibrin-platelet mesh.

Microbiology

• Staphylococcus aureus: Leading cause globally and regionally. Highly virulent, acute destructive presentation, attacking both normal native and prosthetic valves, and prevalent in intravenous drug users (frequently right-sided/tricuspid valve involvement).
• Viridans Group Streptococci (S. mutans, S. mitis, S. oralis): Normal oral flora; common cause of subacute endocarditis on abnormal or damaged native valves following dental manipulation.
• Enterococcus faecalis / faecium: Associated with older patients following gastrointestinal or genitourinary manipulations.
• Coagulase-Negative Staphylococci (Staphylococcus epidermidis): Predominant organism in prosthetic valve endocarditis (PVE) occurring within 12 months of valve surgery.
• Streptococcus gallolyticus (formerly S. bovis): Strongly associated with underlying occult colorectal adenomas or adenocarcinoma; identification mandates colonoscopy.
• HACEK Organisms (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella): Fastidious, slow-growing Gram-negative oral bacteria causing culture-negative endocarditis.

The Modified Duke Diagnostic Criteria

Diagnosis is established clinically when patients satisfy: 2 Major criteria, OR 1 Major + 3 Minor criteria, OR 5 Minor criteria.

• Major Criteria:
  1. Blood Cultures Positive for IE:
     • Typical microorganisms consistent with IE from 2 separate blood cultures (Viridans streptococci, S. bovis, HACEK, S. aureus, or community-acquired enterococci in the absence of a primary focus); OR
     • Microorganisms consistent with IE from persistently positive blood cultures (>= 2 cultures drawn > 12 hours apart, or all of 3, or majority of >= 4 separate cultures); OR
     • Single positive blood culture for Coxiella burnetii or phase I IgG antibody titer > 1:800.
  2. Evidence of Endocardial Involvement:
     • Echocardiographic confirmation (oscillating intracardiac mass/vegetation on valve or supporting structures; myocardial abscess; or new partial dehiscence of a prosthetic valve); OR
     • New pathological valvular regurgitation (worsening or changing of pre-existing murmur is not sufficient).
• Minor Criteria:
  1. Predisposition: Predisposing heart condition (prosthetic valve, prior IE, congenital heart disease, rheumatic valve disease) or intravenous drug use.
  2. Fever: Core body temperature >= 38.0 C (100.4 F).
  3. Vascular Phenomena: Major arterial emboli, septic pulmonary infarcts, mycotic aneurysms, intracranial hemorrhage, conjunctival hemorrhages, and Janeway lesions (painless, erythematous macular lesions on palms and soles).
  4. Immunological Phenomena: Glomerulonephritis, Osler nodes (painful, violaceous subcutaneous nodules on finger/toe pads), Roth spots (retinal hemorrhages with pale central fibrin plugs), and positive rheumatoid factor.
  5. Microbiological Evidence: Positive blood culture not meeting major criteria, or serological evidence of active infection with an organism compatible with IE.

Diagnostic & Therapeutic Approach

• Blood Cultures: In stable suspected IE, obtain 3 blood-culture sets from separate venipunctures before antibiotics, typically over about an hour. If septic or unstable, collect cultures rapidly and start antibiotics promptly; do not wait an hour solely to space samples. Transesophageal echocardiography (TEE) is substantially more sensitive (> 90%) than transthoracic echocardiography (TTE, ~60%) for detecting small vegetations (< 5 mm), perivalvular abscesses, and prosthetic valve involvement.
• Empiric Antimicrobial Regimens (administered after blood cultures are drawn):
  • Community-Acquired Native Valve or Late Prosthetic Valve IE (>= 12 Months): One ESC 2023 option is ampicillin 12 g/day IV in 4–6 doses plus ceftriaxone 2 g IV every 12 hours. Select empirical therapy with the Endocarditis Team using local resistance, allergy and renal function; narrow treatment when cultures identify the organism.
  • Early Prosthetic Valve Endocarditis (<12 months): An ESC 2023 adult option is vancomycin 30 mg/kg/day IV in 2 doses, gentamicin 3 mg/kg/day IV once daily, and rifampicin 900–1200 mg/day in 2–3 doses. Add rifampicin after 3–5 days of effective therapy once bacteraemia clears. Individualize treatment with the Endocarditis Team, renal monitoring and drug levels.
• Dental IE Prophylaxis (AHA): Reasonable for prosthetic valves or prosthetic valve-repair material, previous IE, unrepaired cyanotic congenital heart disease or repaired disease with residual shunt/regurgitation adjacent to prosthetic material, and cardiac transplant with regurgitation from a structurally abnormal valve. The dental procedure must involve gingival/periapical manipulation or oral-mucosal perforation. Give amoxicillin 2 g orally 30–60 minutes before; for penicillin allergy, azithromycin 500 mg orally is an alternative. Clindamycin is no longer recommended for dental prophylaxis.

Epidemiology & Pharmacotherapy of Hypertension in the Caribbean

Hypertension is a major cause of cardiovascular and renal disease in Caribbean practice. The Jamaica Health and Lifestyle Survey 2016–2017 estimated hypertension in 34% of Jamaicans aged 15 years and older; this is a dated Jamaican estimate, not a uniform Caribbean prevalence. Complications include hypertensive nephropathy, stroke and heart failure.

Population Patterns and Individual Treatment

Low-renin hypertension and salt sensitivity are common in populations of African ancestry, but do not define every individual. Dietary sodium reduction remains important. CCBs and thiazide-like diuretics are effective options; ACE inhibitors and ARBs also have first-line and disease-specific roles. Choose treatment using the patient’s BP, diabetes, albuminuric CKD, heart failure, contraindications and response, following the applicable guideline.

Evidence-Based Pharmacotherapy Guidelines

1. First-Line Antihypertensive Agents:
   • Calcium Channel Blockers (Dihydropyridines): E.g., Amlodipine (5 to 10 mg once daily). Promotes potent peripheral arteriolar vasodilation independent of renin status; proven superior in stroke reduction.
   • Thiazide-like Diuretics: E.g., Chlorthalidone (12.5 to 25 mg daily) or Indapamide (1.5 to 2.5 mg daily); hydrochlorothiazide (12.5 to 25 mg daily) is widely used. Preferred over traditional loop diuretics for hypertension due to sustained 24-hour half-life and independent direct vasodilatory actions.
   • Initial choices include a long-acting CCB, thiazide-like diuretic, ACE inhibitor or ARB. NICE favors a CCB for Black African/African–Caribbean adults without type 2 diabetes; diabetes and other comorbidities change selection.
2. Combination Therapy:
   • Most patients with baseline blood pressure >= 20/10 mmHg above target require two first-line agents of different classes from the outset.
   • Recommended core combination: CCB + Thiazide-like Diuretic, or CCB + ARB / ACEi.
   • If chronic kidney disease (CKD) with proteinuria is present, an ACEi or ARB must be included to reduce intraglomerular pressure and retard nephropathy progression.
3. Resistant Hypertension:
   • Defined as blood pressure that remains above goal (>= 140/90 mmHg) despite the concurrent use of three antihypertensive agents of different classes at optimal doses, one of which must be a diuretic.
   • Workup: Exclude pseudo-resistance (medication non-adherence, white-coat hypertension, inappropriate cuff size) and secondary etiologies (obstructive sleep apnea, primary aldosteronism [elevated aldosterone-renin ratio], renal artery stenosis, chronic kidney disease, Cushing syndrome, pheochromocytoma).
   • Preferred Fourth-Line Agent: Low-dose Spironolactone (25 to 50 mg daily), targeting aldosterone-mediated sodium retention.

Hypertensive Emergencies vs. Hypertensive Urgencies

Severe acute blood pressure elevation (typically systolic BP >= 180 mmHg and/or diastolic BP >= 120 mmHg) is bifurcated into two distinct clinical entities based on the presence of acute, ongoing Target Organ Damage (TOD):

+-----------------------------------------------------------------------------------------+
|                        Severe BP Elevation (>= 180 / >= 120 mmHg)                       |
+-----------------------------------------------------------------------------------------+
                                             |
                   +-------------------------+-------------------------+
                   |                                                   |
                   v                                                   v
       [ Acute Target Organ Damage ]                       [ NO Target Organ Damage ]
                   |                                                   |
                   v                                                   v
         HYPERTENSIVE EMERGENCY                             HYPERTENSIVE URGENCY
                   |                                                   |
         - ICU Admission                                    - Outpatient / Ward setting
         - IV Pharmacotherapy                               - Oral Antihypertensives
         - Controlled reduction of MAP:                       (Amlodipine, Labetalol, Clonidine)
           <= 20-25% in 1st hour                            - Gradual reduction over 24-48 h
           to ~160/100 mmHg over 2-6 h                      - Sublingual nifedipine BANNED

Clinical Manifestations of Target Organ Damage

• Neurological: Hypertensive encephalopathy (headache, vomiting, papilledema, altered mentation, seizures); acute ischemic stroke; acute intracerebral or subarachnoid hemorrhage.
• Cardiovascular: Acute aortic dissection (severe tearing chest/back pain, pulse deficit); acute coronary syndrome (STEMI/NSTEMI); acute pulmonary edema with left ventricular failure.
• Renal: Acute hypertensive nephrosclerosis, acute kidney injury with hematuria and red cell casts.
• Obstetric: Severe pre-eclampsia or eclampsia (hypertension, proteinuria, seizures, HELLP syndrome).
• Ophthalmologic: Grade III/IV Keith-Wagener-Barker retinopathy (flame hemorrhages, cotton-wool spots, bilateral papilledema).

Blood Pressure Lowering Targets & Rates

Autoregulation maintains constant cerebral and renal blood flow across a mean arterial pressure (MAP) range of approximately 60 to 120 mmHg. In chronic hypertension, the autoregulatory curve shifts rightward. Rapid or excessive blood pressure reduction causes cerebral, myocardial, and renal perfusion to fall precipitously below the autoregulatory threshold, inducing watershed cerebral infarction, acute coronary ischemia, or acute tubular necrosis.

• Usual Protocol When No Condition Requires a Different Target:
  • Reduce Mean Arterial Pressure (MAP = DBP + 1/3[SBP - DBP]) by no more than 20% to 25% within the first hour.
  • If clinically stable, lower blood pressure toward 160/100 to 110 mmHg over the subsequent 2 to 6 hours.
  • Normalize toward target levels gradually over the following 24 to 48 hours.
• Critical Exceptions to the Gradual Rule:
  1. Acute Aortic Dissection: Mandates rapid reduction of SBP to < 120 mmHg and heart rate to < 60 bpm within 20 minutes. Administer an IV beta-blocker (Esmolol or Labetalol) before any vasodilator to eliminate reflex tachycardia, which increases aortic wall shear stress (dP/dt).
  2. Acute Ischemic Stroke: Without IV thrombolysis or thrombectomy and without another urgent indication, usually withhold acute antihypertensive therapy if BP is < 220/120 mmHg. For IV thrombolysis, reduce BP to < 185/110 before treatment and maintain <= 180/105 afterwards. Before thrombectomy without thrombolysis, BP <= 185/110 is reasonable; use the stroke-team protocol thereafter. Severe hypertension in pregnancy also needs prompt treatment from 160/110 mmHg rather than this general gradual protocol.

Intravenous Pharmacotherapy in Hypertensive Emergencies

• Labetalol: Combined alpha-1 and non-selective beta-blocker (1:7 alpha-to-beta ratio IV). Dose: 10-20 mg IV bolus over 2 minutes, repeated or doubled every 10 minutes (up to 300 mg), or continuous infusion at 0.5-2 mg/min. Excellent safety profile in encephalopathy, stroke, aortic dissection, and pre-eclampsia. Contraindicated in severe asthma, high-degree AV block, and acute decompensated heart failure.
• Nicardipine: Dihydropyridine CCB. Dose: 5 mg/h IV infusion, titrated by 2.5 mg/h every 5 to 15 minutes (maximum 15 mg/h). Highly predictable arterial dilation without depressing myocardial contractility.
• Hydralazine: Direct arteriolar vasodilator and an option for severe hypertension in pregnancy. Give 5 mg IV slowly; reassess and repeat 5–10 mg every 20–40 minutes if needed, to 20 mg cumulative. Monitor for maternal hypotension, reflex tachycardia and fetal heart-rate abnormalities.
• Sodium Nitroprusside: Balanced arteriolar and venous vasodilator. Rapid onset and offset. Carries risk of cyanide and thiocyanate toxicity with prolonged (> 24-48 h) or high-dose (> 2 mcg/kg/min) infusions, especially in renal or hepatic impairment.