AZ Guide u Cardiology

Abciximab (ReoPro®)

  • Abciximab is an agent for use in patients undergoing percutaneous coronary intervention.
  • It acts by binding to glycoprotein (GP) IIb/IIIa and inhibits platelet aggregation.
  • Several trials (EPIC,EPILOG and CAPTURE) have demonstrated that Abciximab is safe and effective in reducing the number of thrombotic ischemic events after percutaneous coronary intervention.

ADENOSINE

  • Adenosine is an endogenous purine nucleoside which, when injected intravenously, causes transient heart block by slowing atrioventricular nodal conduction.
    This makes it highly effective for termination of paroxysmal supraventricular tachycardia with re-entrant circuits that include the atrioventricular node.
  • Adenosine has a very short half-life: less than 2 seconds.
  • Transient side effects, including:
  • chest discomfort,
  • dyspnoea,
  • flushing

are common with Adenosine.

  • Adenosine is also used as a diagnostic aid to establish the correct diagnosis in the tachycardia with broad QRS complexes.

u ADR / ADENOSINE

  • Proarrhythmic effect of Adenosine in a patient with atrial flutter.

A patient with a narrow complex tachycardia with a ventricular rate of 140 beats/min which was unresponsive to Amiodarone 400 mg i.v
Adenosine was given to distinguish possible atrial flutter with a 2:1 block from an AV re-entrant tachycardia.
15 seconds after Adenosine 20 mg administration, the patient experienced a transient increase in AV block then developed 1:1 AV conduction with a ventricular rate of 260 beats/min.

[Slade AKB, Garratt CJ. British Heart J 1993; 70: 91-92]

  • Adenosine-induced non-sustained polymorphic ventricular tachycardia.

A patient treated with Adenosine 6 mg i.v. for supraventricular tachycardia had a short run of non-sustained polymorphic ventricular tachycardia. Heart rate was 180 beats/min.
Authors recommend that:
"instruments for resuscitation, including a DC-cardioverter, are mandatory when Adenosine is administered".

[Romer M, Candinas R. European Heart J 1994; 15: 281-282]

AMIODARONE

  • Amiodarone is a class III antiarrhythmic agent with no relevant negative inotropic effects and may be used in patients with reduced LVEF when other antiarrhythmics are contraindicated.
  • Amiodarone has peculiar pharmacokinetics properties: the volume of distribution of Amiodarone is extremely large (60 liters/Kg) because of the deposition in adipose tissue and highly perfused organs.
    After discontinuation of Amiodarone, the plasma half-life varies from 26 to 107 days, with a mean of approximately 53 days.
    The major matabolite is desethylamiodarone, which has a longer half-life of the parent drug.
  • The use of Amiodarone is associated with numerous adverse reaction:

a) cardiac side effects.

The incidence of proarrhythmic effects caused by Amiodarone administration appears low.
The most frequent cardiac effect is a dose-dependent symptomatic sinus bradycardia.
Bradycardia seems to be more common in patients with pre-existing bradycardia-tachycardia syndrome.
The potential to exacerbate or induce congestive heart failure has been demonstrated. It is, however, difficult to separate spontaneous from Amiodarone-induced deterioration.

b) pulmonary toxicity,

biopsies and autopsies have demonstrated interstitial and alveolar fibrosis and inflammation.

c) hepatic toxicity,

consisting in elevations in liver enzyme levels.
Discontinuation of the drug is recommended if the liver enzyme concentrations exceed three times normal.

d) corneal microdeposits,

5-10% of patients will observe halos or blurred vision.
The corneal microdeposits are reversible on stopping the drug.

e) photosensitization,

occurring in approximately 10% of patients.
With continued treatment the skin assumes a blue-gray coloration.
The discoloration of the skin regresses slowly after discontinuation of Amiodarone.

f) alterations in thyroid function.

Amiodarone contains 37% iodine (75 mg iodine per 200 mg tablet).
Amiodarone:

  • increases T4 and reverse T3
  • decreases slightly T3

Thyroid dysfunction caused by Amiodarone may be difficult to recognise symptomatically.

  • Bradycardia and costipation are common features associated both with Amiodarone use and hypothyroidism.
  • Tremor, myopathy and sleep disturbance are associated both with Amiodarone use and hyperthyroidism.

u INTERACTIONS

Amiodarone has been found to interact with numerous drugs.
Because of slow elimination, its potential for interaction with another agent persists for months after it is discontinued.

Pharmacokinetic interactions

Digoxin Increased Digoxin concentration
Flecainide Increased Flecainide concentration
Phenytoin Increased Phenytoin concentration
Procainamide Increased Procainamide concentration
Quinidine Increased Quinidine concentration
Warfarin Increased Warfarin concentration

Pharmacodynamic interactions

Beta-blockers Bradycardia
Calcium-antagonists
(Diltiazem, Verapamil) 		Bradycardia and Hypotension
Quinidine Torsades de Pointes

u AMIODARONE - WITHDRAWAL PROBLEM

The need to withdraw Amiodarone creates a difficult clinical problem.
If Amiodarone is withdrawn because of side-effects, its antiarrhythmic effect may persist for weeks or months.
Hospitalization is the safest approach to this problem, with intermittent sampling of the plasma concentration of Amiodarone.
An alternative approach is to check if QT interval is returned to normal value.

u ADR / Adverse Drug Reaction / Amiodarone

  • Ventricular fibrillation after intravenous Amiodarone in Wolff-Parkinson-White syndrome with atrial fibrillation.

The patient was admitted to hospital with a syncopal episode.
ECG showed atrial fibrillation with ventricular pre-excitation and a high ventricular rate.
Intravenous Amiodarone (5 mg/Kg per 20 min) was administered.
A few minutes after the 20-min infusion, the patient collapsed in ventricular fibrillation.
Prompt application of DC shock (200J) restored sinus rhythm.

[Boriani G. et al, Am Heart J 1996; 131: 1214-1216]

  • Acute pancreatitis

Amiodarone can induce acute pancreatitis, which seemed not to be related to cumulative dose or duration of therapy.
It was probably an idiosyncratic-type reaction.
A patient (46 year old) treated for atrial fibrillation secondary to rheumatic mitral stenosis, presented nausea, vomiting and epigastric pain after 4 days of Amiodarone (800 then 400 mg/day).
Pancreatic enzymes were increased.
Amiodarone was discontinued and replaced with Procainamide. Five days later serum pancreatic isomylase and lipase levels returned to normal.

(Lancet 1997; 350:1300)

  • Torsade de Pointes

Although the incidence of Torsade de Pointes (TdP) during oral Amiodarone therapy has been reported to be low (< 1%), it constitutes a potentially life-threatening, clinically important side effect.
The women seem to be at an increased risk of developing TdP secondary to Amiodarone.
In contrast to other agents known to prolong QT, TdP associated to Amiodarone do not occur after a single dose or early after initiation of therapy.
Torsade de Pointes develops either towards the end of the loading phase or during chronic therapy.
Thus, electrocardiographic changes should be closely monitored towards the end of the loading phase.

[Eur Heart J 1998; 19: 189A]

ATHEROSCLEROTIC PLAQUES

Acute thrombosis after atherosclerotic plaque disruption is a major complication of primary atherosclerosis leading to acute ischemic syndromes and atherosclerosis progression.

Endothelial disruption and damage to the normal vessel may expose subendothelial procoagulant molecules, including tissue factor, which complexes with factor VII / VIIa in flowing blood, cleaving FIX and FX with subsequent fibrin deposition.

ATORVASTATIN

  • Atorvastatin is HMG-CoA reductase inhibitor.
  • It is indicated to reduce elevated total cholesterol, LDL-C, apo B and triglycerides.
  • It is recommended that liver function tests be performed prior to and at 12 weeks following both the initiation of therapy and any elevation of dose, and periodically thereafter.
  • Atorvastatin is contraindicated in patients with active liver disease or unexplained persistent elevations of serum transaminases; in women during pregnancy and in nursing mother.
  • Atorvastatin therapy should be temporarily withheld or discontinuated in any patient with an acute, serious condition suggestive of a myopathy or having a risk factor predisposing to the development of renal failure secondary to rhabdomyolysis

ATRIAL FIBRILLATION

  • Atrial Fibrillation is one of the most common cardiac arrhythmias with a prevalence of about 0.4% in the general population.
  • It is even more prevalent in elderly persons, especially those with underlying heart disease.
  • Termination of the atrial fibrillation with restoration of sinus rhythm may improve cardiac performance and exercise tolerance.

u CONVERSION TO SINUS RHYTHM

a) Propafenone better than Amiodarone

Propafenone results in earlier reversion to sinus rhythm than Amiodarone.
This is due to the particular pharmakinetics of Amiodarone.
Intravenous Propafenone is the first-line agent for cardioversion for a recent onset of atrial fibrillation in patients without left ventricular dysfunction or acute myocardial infarction. In these selected patients, Amiodarone could be considered the drug of choice.

  • Negrini M. et al. A comparison of propafenone and amiodarone in reversion of recent-onset atrial fibrillation to sinus rhythm. Current Therapeutic Research 1994; 55: 1345-1354.
  • Larbuisson R. et al. The efficacy and safety of intravenous propafenone versus intravenous amiodarone in the conversion of atrial fibrillation or flutter after cardiac surgery. J Cardiothorac Vasc Anesth 1996; 10: 229-34
  • Fresco C., Proclemer A. Clinical challenge II. Management of recent onset atrial fibrillation. PAFIT-2 investigators. Eur Heart J 1996; 17 (Suppl C): 41-47.

b) Direct current cardioversion
  • DC cardioversion is the therapy of choice for haemodynamically compromised patients with paroxysmal atrial fibrillation (AF) and paroxysmal supraventricular tachycardia (SVT).
  • An alternative approach could be Amiodarone.
    Amiodarone infusion may be given at the dosage of 150 mg in 10 minutes.
    The second Amiodarone dosage (150 mg in 10 min) may be given 30-35 min after the first if the arrhythmia was persisting.

c) Low energy internal cardioversion

Sinus rhythm can be restored in a proportion of patients with atrial fibrillation in whom conventional thoracic shocks have failed, using biphasic shocks delivered between the right atrium and the coronary sinus.
The energy required is very low, and general anesthesia is not required.

d) Risk for embolic stroke

Cardioversion with rapid return of sinus rhythm is associated with a risk for embolic stroke.
The transoesophageal echocardiography [TEE]-guided approach to cardioversion with short-term (heparin or warfarin < 24h) anticoagulation therapy can represent an alternative to conventional therapy.
These the conclusions of ACUTE (Assessment of Cardioversion Using Transesophageal Echocardiography) pilot study.

[Klein AL et al., Annals of Internal Medicine 1997; 126: 200-209]

e) Atrial fibrillation complicating open-heart surgery

Atrial fibrillation is a frequent complication of open-heart surgery, being reported in about 25% to 30% of patients.
Although the arrhythmia is frequently short-lived and reverts spontaneously, the rapid ventricular rate and the loss of atrial contraction can be particularly detrimental in the early postoperative period, so that a quick restoration of sinus rhythm is usually desirable.
Several agents have been used in this setting: verapamil, digoxin and beta-blockers slow the ventricular rate but are seldom able to restore sinus rhythm.
In 50 patients who develop atrial fibrillation within 48 hours after open-heart surgery, intravenous Propafenone (2 mg/Kg in 10 minutes) was administered 15 minutes after the onset of the arrhythmia.
Sinus rhythm was restored in 35 patients (70%) after a mean time of 22+6 minutes after the beginning of the infusion.

Conversion rate with Propafenone i.v. (2mg/kg)
  • coronary artery bypass graft
  • valvular or septal surgery

88%
39%

In those whose arrhythmia did not convert to sinus rhythm, the ventricular rate was reduced from 142 + 14 beats/min to 108 + 9 beats/min (p <0.01).

In patients whose arrhythmia was converted to sinus rhythm, mean cardiac index increased from a mean baseline value of 2.7 + 0.4 L/min/m2 to 3.4 + 0.1 L/min/m2 (p <0.05), while it remained virtually unchanged in those whose arrhythmia did not convert.

No significant side effects were observed.

[Gentili C. et al, Am Heart J 1992; 123: 1225-1228]

ATRIAL FLUTTER
Electrical cardioversion & risk of thromboembolism

Patients with atrial fibrillation undergoing cardioversion are at increased risk of embolic events, while those with atrial flutter have traditionally been considered to be at low risk due to the presence of organised atrial activity.
However, recent studies have demonstrated that atrial thrombus and spontaneous echo contrast may occur in patients with atrial flutter.

[Irani WN et al (Circulation 1997; 95: 962-966)].

AZIMILIDE

  • Azimilide is a class III antiarrhythmic agent which blocks both the slowly-and-rapidly-activating components of the delayed rectifier outward potassium current.
  • Azimilide has a long half life as excretion of unchanged azimilide up to 4 days following administration.
  • A trial, ALIVE, in 6,000 patients who have survived to a heart attack has begun.

[FASEB J, 1997; 2281,9]

CORONARY ATHEROSCLEROSIS / Chlamydia pneumoniae

  • Chlamydia pneumoliae seems to play a role in the pathogenesis of atherosclerosis.
  • In the study of Alaska Natives (Circulation 1998; 98: 628-633), the evidence for infection preceding or accompanying early asymptomatic lesions in young, low-risk adults is consistent.

DOFETILIDE

  • Dofetilide is an Class III antiarrhythmic agent, acting as a cardioselective potassium channel antagonist by delaying myocardial repolarisation.
  • Dofetilide may cause Torsades de Pointes and the patients should be monitored very closely in hospital for the first few days to pick up the proarrhythmic effects.

u DIAMOND - CHF Trial

DIAMOND - CHF Trial involved 1,518 patients with heart failure and ventricular arrhythmias. Dofetilide did not increase the mortality:

 

Pts. treated (n°)

Deaths (n°)
  • Dofetilide

762

311
  • Placebo

756

317

Dofetilide had no effect on arrhythmic death and was associated with a higher risk of ventricular arrhythmia than placebo (7.8% vs 4.3%).
Torsades de Pointes occurred in 25 patients in the Dofetilide-treated group (none in the placebo group).
DIAMOND-CHF Trial suggest that Dofetilide would not be practical for routine treatment of heart failure patients.
In patients with heart failure and arrhythmias Amiodarone is currently the drug of choice.

u DIAMOND-MI Trial

The results of DIAMOND-MI Trial did not show a mortality benefit for Dofetilide.
Post-myocardial infarction patients have a high risk of sudden death.

u DOFETILIDE IN THE MANAGEMENT OF ATRIAL FIBRILLATION

Atrial fibrillation is a no-life-threatening arrhythmia and Dofetilide causes serious proarrhythmic effects (Torsades de Pointes).

FETAL SUPRAVENTRICULAR TACHYCARDIA

  • Fetal supraventricular tachycardia is a rare condition which may lead to hydrops fetalis (fluid accumulation in 2 body cavities).
  • Intrauterine antiarrhythmic drug therapy is an effective treatment. However, the incidences of premature delivery, morbidity and mortality associated with the arrhythmia are still high.

FLECAINIDE

  • Flecainide belongs to class IC antiarrhythmic agents according to the classification by Vaughan-Williams, as its major electrophysiologic effect is sodium-channel blockade.
  • At the beginning, Flecainide was indicated in the management of ventricular arrhythmias, but after the results of CAST (Cardiac Arrhythmia Suppression Trial) this use was discontinued.
  • In 1989 the CAST study showed that there were some patients populations in which Flecainide might paradoxically increase the risk of arrhythmic death; in patients with a recent myocardial infarction and premature ventricular beats, treatment with Flecainide was associated with a 2.5-fold increase in mortality compared with placebo treatment.

[ N Engl J Med 1989; 321: 406-412]

  • Flecainide is an effective drug for the conversion of atrial fibrillation to sinus rhythm.
  • A controlled study compared the efficacy and tolerability of Flecainide and Propafenone for the conversion of paroxysmal atrial fibrillation or flutter to sinus rhythm, within 1 hour of drug administration.

In atrial flutter these drugs exert almost no effect.
At a dose of 2 mg/Kg in 10 min, Flecainide is more effective than Propafenone for conversion of paroxysmal atrial fibrillation to sinus rhythm

 

Flecainide

Propafenone

Conversion rate

  • atrial fibrillation
  • atrial flutter

90%
20%

55%
40%

Side effects

  • dizziness
  • paraesthesia
  • dryness of mouth
  • hypotension
  • left bundle brach block
  • junctional escape rhythm

2
5
1
1
1
2

2

[Suttorp MJ et al., J Am Coll Cardiol 1990; 16: 1722-1727]

  • The tolerability of Flecainide for the prevention of atrial fibrillation and atrial flutter has been assessed in a double-blind crossover study.
Side effects

Flecainide
(events)
Dizziness
Gastrointestinal reactions
Eye disturbances
Cardiovascular complaints
Tiredness
Amenorrhoea
Dry mouth
Tingling scalp
Urge incontinence
Paraesthesia
Tinnitus
Flushing
Headache

11
12
11
6
3
1
1
1
1
1
1
1
1

[Pietersen AH et al. Am J Cardiol 1991; 67: 713-717]

u FLECAINIDE IN THE MANAGEMENT OF FETAL SUPRAVENTRICULAR ARRHYTHMIAS

The development of fetal tachycardia and heart failure in utero is a life-threatening condition with a reported mortality rate of 20-50%.
Flecainide, administered orally to the mother, achieved therapeutic drug concentrations in the fetus quickly and stopped the supraventricular arrhythmias.

[Allan L.D. et al. British Heart Journal 1991; 65: 46-48]

u FLECAINIDE AND AMIODARONE INTERACTION

Amiodarone produces a rise in Flecainide plasma level.
The Authors suggest that reducing the daily dose of Flecainide by one-third during combined treatment allows the maintenance of plasma levels in the range of those obtained with full doses of monotherapy.
However, in view of the wide range of individual variations, it is imperative to measure serial plasma Flecainide levels during the initial period of combined therapy to avoid toxic complications or, conversely, underdosing.

[Sea P. et al. JACC 1986; 7: 1127-30]

GLICOPROTEIN IIb/IIIa INHIBITORS

  • GP IIb/IIIa antagonists are able to prevent repeat vessel occlusion after PTCA complicated by subsequent threatened or abrupt vessel closure.
  • The cause of abrupt closure is often intimal dissection or platelet-rich thrombus.

HYPERHOMOCYSTEINAEMIA

  • Hyperhomocysteinaemia is a mayor and independent risk factor for vascular disease, and venous thrombosis.
  • High concentrations of homocysteine are found in up to 30% of patients with atherosclerosis and concentrations only 12% above the upper limit of normal (15 m mol/L, mild hyperhomocysteinaemia) are associated with a three-fold increase in the risk of acute myocardial infarction.
  • Homocysteine concentrations are determined by:

a) genetic factors
(mutations in the genes for enzymes involved in homocysteine metabolism)

b) nutritional factor
(deficiencies of vitamin B6, B12 and folic acid)

  • The mechanisms by which hyperhomocysteinaemia promotes atherosclerosis are not fully understood.
    In vitro studies show that exposure of endothelial cells to homocysteine results in oxidative effects, including generation of superoxide anion radicals and hydrogen peroxide, which lead to inactivation of nitric oxide and endothelial cell damage.
    The resultant endothelial dysfunction may then contribute to vasospasm, thrombosis and progression of atherosclerosis.

IBUTILIDE

  • Ibutilide is a Class III antiarrhythmic agent.

u IBUTILIDE FOR THE MANAGEMENT OF ATRIAL FIBRILLATION

H. Shenate et al. (O’Connor Hospital, San Jose, CA, USA) examined the effect of Ibutilide infusion (1-2 mg over 10-30 minutes) in 28 consecutive patients with atrial fibrillation (af) and Afl (atrial flutter) [16 males, 12 females; aged 41-79 years].

  • Conversion to sinus rhythm 57% (16 of 28 patients)
  • Proarrhythmia 36% (10 patients)

Proarrhythmic effect were classified as:

- Torsade de Pointes 7 pts
- monomorphic nonsustained VT 2 pts
- sustained VT 1 pts

Six patients with proarrhythmia manifestation, required intervention.
No electrolyte imbalance or apparent active ischemia was present.

According to Authors:

  • incidence of Ibutilide-induced proarrhythmia is higher than previously reported;
  • female gender is predominant in patients who developed proarrhythmias;
  • caution should be exercised when using Ibutilide and CPR measures, including a defibrillator , should be readily available.

[ Shenasa et al. Circulation 1997; 96 (8): I-383].

IMPLANTABLE DEFIBRILLATOR

u INTERFERENCE BY AN ELECTRONIC ANTITHEFT-SURVEILLANCE DEVICE

Electronic antitheft-surveillance devices, which are widely used in stores, libraries and other places to prevent theft, are a potential source of electromagnetic interference.
Electromagnetic interference with implantable defibrillators can generally be divided into 4 types:

1) overcounting of the ventricular rate (the most common type).
Misinterpretation of rapid rates may lead to inappropriate antitachycardia pacing or the delivery of shocks;

2) noise-reversion mode, which results in asynchronous pacing and inhibits the detection of true tachycardias and the following defibrillation;

3) inadvertent reprogramming of the functions of the defibrillator;

4) permanent damage to the circuitry.

u THE RAPID CONSECUTIVE SHOCKS FROM ICD SYSTEMS MAY RESULT IN MYOCARDIAL INJURY

12 patients undergoing tranvenous ICD implantation were studied:

 

Patients

Indication for ICD therapy:

  • ventricular tachycardia
  • ventricular fibrillation

Underlying cardiac disease:

  • coronary artery disease
  • aortic stenosis
  • Prinzmetal’s angina
  • dilated cardiomyopathy

7
5

9
1
1
1

Mean ejection fraction: 35.33 + 10,4%

In all patients, multiple shocks were administered for the purpose of defibrillation threshold determination.
Shock energies for defibrillation threshold testing ranged from 6 to 34J.
The number of shocks in all patients ranged from 5 to 16 (mean 6 + 2) with a total cumulative energy from 36 to 418J (mean 112 + 57).

Cardiac troponin I was measured.
5 of 12 patients (42%) had elevation of cardiac troponin I with peak levels within the first 12 hours.
The elevations of cardiac troponin I, as the result of multiple endocardial countershocks, reflect injury to the heart.

[Joglar J. A. et al. Am J Cardiol 1999; 83: 270-272]

INTERMITTENT CLAUDICATION

  • Many agents have been tried for the management of intermittent claudication, although few drugs have demonstrated efficacy in placebo-controlled trials.
    The include: rheological agents, vasodilators, antiplatelet agents, anticoagulants, prostaglandins and prostaglandin analogs.
  • Pentoxifylline has been the most extensively evaluated drug for claudication.
    Pentoxifylline has failed to consistently demonstrate important clinical benefit in controlled clinical trials.

LONG QT SYNDROME

  • The "long QT syndrome" results from mutations in HERG, a gene that encodes subunits of the potassium channel that modulates extracellular potassium.
    b -blockers and permanent pacing are used to prevent sudden death in these patients.
    However, these therapies do not correct the repolarisation abnormalities and impaired functioning of the potassium channel.
  • The long QT syndrome is a familial disease characterized by an abnormally prolonged ventricular repolarization and a high risk of malignant ventricular tachiarrhythmias.
    Under the clinical point of view, we can identify two variants:
  • Romano-Ward syndrome
  • Jervell and Lange-Nielsen syndrome

Romano-Ward Syndrome

Five loci have been associated with the Romano-Ward long QT syndrome and they are located on chromosomes 3,4,7,11 and 21 and so far four genes have been identified:

New terminology

    

LQT3

SCN5A

Encoding the cardiac sodium channel (chromosome 3)

LQT2

HERG

Encoding the Ikr potassium channel protein (chromosome 7)

LQT1

KvLQT1

Encoding the a subunit of the Iks potassium channel protein (chromosome 11)

LQT5

KCNE1

Encoding mink, an ancillary subunit for the Iks channel complex (chromosome 21)

Jervell and Lange-Nielsen Syndrome

This syndrome arises in individual who inherit abnormal KvLQT1 or mink alleles from both parents.

Drug-induced long QT Syndrome

The hypothesis that drug-induced long QT Syndrome might be due to "silent" mutations on long QT syndrome (LQT) genes is collecting new evidences.
These alterations are insufficient to prolong the QT interval at rest, but may be sensitive to any drugs that slow K+ currents.

Familial hypertrophic cardiomyopathy

Familial Hypertrophic Cardiomyopathy is characterized by a genetic heterogeneity.
Mutations in 7 sarcomeric protein genes have been identified:

  • beta-myosin heavy chain on chromosome 14;
  • cardiac essential myosin light chain on chromosome 3;
  • cardiac regulatory myosin light chain on chromosome 12;
  • cardiac troponin T on chromosome1;
  • alpha tropomyosin on chromosome 15;
  • cardiac myosin binding protein-C on chromosome 1;

MARKERS OF MYOCARDIAL LESION

  • The degree of myocardial necrosis may be estimated by the rise of several biochemical markers, CK and CK-MB.
  • The sensitivity and specificity of these markers are low.
  • Cardiac Troponin I (cTnI) has a high cardiac specificity and is the best marker for detecting minor myocardial damage compared to other classical biochemical markers.

[Eur Heart J 1998; 19: 197A]

MENOPAUSE

  • Menopause is considered as an indipendent risk factor for the development of atherosclerosis.
  • Menopause has an unfavorable effect on the female lipidemic profile.
  • Several studies have examined the effect of hormone replacement therapy (HR-T) on menopausal women and have shown a lower cardiovascular and total mortality rate.

Ovarian hormones have several effects upon the cardiovascular system. They could play an integral role in the manteinance and stabilisation of signal transmission within the heart. This effect may be due to the calcium antagonistic properties of 17 beta-estradiol.

[Eur Heart J 1998; 19: 237A]

MYOCARDIAL INFARCTION / ORAL CONTRACEPTIVES

  • In 1991, the National Institute of Child Health and Human Development funded population-based case control studies to assess the relationship of low-dose oral contraceptive use with myocardial infarction (MI).
    A pooled analysis of 2 US studies concluded that low-dose oral contraceptives are safe in relation to risk of MI for healthy women without major CVD risk factors.

(Circulation 1998; 98: 1058-1063)

MYOCARDITIS

Myocarditis is an inflammatory process of the heart, involving myocytes, interstitium, vascular elements or pericardium.
Myocarditis is most commonly characterized by a lymphocytic infiltrate of the myocardium with associated myocyte necrosis (lymphocytic myocarditis).
The role of immunosuppressive therapy in lymphocytic myocarditis is controversial.
A review of the literature shows that immunosuppressive therapy is ineffective in lymphocytic myocarditis.

[Garg A. et al. Ann Intern Med 1998; 128: 317-322].

PREMATURE VENTRICULAR COMPLEXES

  • Isolated monomorphic premature ventricular complex (PVCs) are detected also in healthy subjects using a routine resting ECG.
  • CHILDREN
    •

There is a significant percentage of children with benign ventricular ectopy with associated repolarization abnormalities, as evidenced by a prolonged QTc and/or JTc.
This does not imply that these children have long QT syndrome (LQTS).

RADIOFREQUENCY CATHETER
ABLATION

  • Concerns regarding prolonged radiation exposure and fluoroscopy time remain even if the longterm effects of radiation exposure during radiofrequency catheter ablation are unknown.
  • Inappropriate sinus tachycardia has been frequently reported after radiofrequency ablation for accessory pathway and atrioventricular nodal reentrant tachycardia.
    It is believed to represent autonomic dysfunction secondary to damage of parasympathetic innervation to the sinoatrial node by ablation.
    After 6 weeks the parasympathetic/sympathetic imbalance was resolved with no long term consequence.

[Eur Heart J 1998; 19: 199A]

RESTENOSIS

  • Restenosis after percutaneous transluminal coronary angioplasty (PTCA) is characterized by progressive arterial remodeling, extracellular matrix formation and intimal hyperplasia at the site of angioplasty.
  • Arterial restenosis is a complex biological process initiated by platelet adhesion and aggregation at the site of arterial injury.
  • Platelet activation results in the release of a variety of vasoactive and mitogenic factors that stimulate vascular smooth muscle cell proliferation, matrix formation and the late fibroproliferative response.
  • Arterial restenosis occurs in 20% to 50% of patients within 6 months after PTCA.

RIGHT VENTRICULAR DYSPLASIA

  • In patients with right ventricular dysplasia a spontaneous sustained ventricular tachycardia can occur.
  • An enhanced humoral sympathetic tone seems to be the main determining factor in the occurrence of this tachyarrhythmia.
  • Arrhythmogenic right ventricular dysplasia is often discovered in athletes, who may achieve an high level of stimulation of the sympathetic system during the exercise to modify their ventricular tachycardia substrate.

SICK SINUS SYNDROME

  • Patients with the sick-sinus syndrome and no signs of atrioventricular conduction abnormalities should be treated with atrial pacing instead of ventricular pacing because atrial pacing is associated with lower mortality, less atrial fibrillation, thromboembolic complications, heart failure, and a low-risk of atrioventricular block.

[Andersen HR et al., Lancet 1997; 350: 1210-1216].

SOTALOL

Sotalol is a beta-adrenergic blocking drug with Class III antiarrhythmic properties.

u Sotalol reduces the incidence of recurrences of sustained ventricular tachiarrhythmias.

146 consecutive patients with inducible sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) were enrolled.
In 53 patients Sotalol prevent induction of VT/VF during electrophysiological testing.
In 93 patients, tachyarrhythmias remained inducible and an implantable cardioverter defibrillator (ICD) was implanted.
After implantation of the device the patients were randomised to two groups: ICD / Sotalol group and ICD group.
All patients were followed-up for > 1 year.
80 mg Sotatol was administered as initial daily dose. If tolerated, the dose was increased in steps of 80 mg per 24h up to 400 mg per 24h.

Results:

 

Sotalol
(n = 53)

Sotalol + ICD
(n = 46)

ICD
(n = 47)
  • Recurrence of ventricular tachycardia
  • Recurrence of ventricular fibrillation

18,8%
5,6%

19,6%
10,9%

36,2%
14,9%

Total mortality was not different between the 3 groups.

[Kühlkamp V. et al, J Am Coll Cardiol 1999; 33: 46-52]

STATINS (HMG-CoA REDUCTASE
INHIBITORS)

u INTERACTIONS

  • Cyclosporine

The statins should be used cautiously in patients on concomitant treatment with Cyclosporine because of increased risk of myositis and rhabdomyolysis (RAB).
The incidence of RAB is however low, mainly asymptomatic and with good prognosis after withdrawal of statins.

[Eur Heart J 1998; 19: 190A]

THROMBOSIS

  • Thrombosis-related heart disease, including unstable angina, acute myocardial infarction is a leading cause of death worldwide.
  • Blood platelets play a key role in thrombosis formation.
    In response to vascular injury, typically occurring at the site of an atherosclerotic plaque in a coronary artery, thrombosis is initiated as platelets pass through three key steps:
  • adhesion to the injured endothelium;
  • activation by one or more agonists, including ADP, epinephrine, thrombin and thromboxane A2, which are secreted at the site of injury;
  • aggregation: the platelets bind fibrinogen to form interplatelet bridges, resulting in a dense platelet plug.

During the activation phase, changes in platelets occur. The most important is a structural change in the GP IIb/IIIa receptor that exposes fibrinogen binding sites.

TIROFIBAN

  • Tirofiban is a reversible, nonpeptide GP IIb/IIIa platelet receptor blocker.
  • Tirofiban is indicated for unstable angina or non-Q-wave myocardial infarction.
  • Tirofiban is controindicated in patients with:
  • active internal bleeding
  • intracranial pathology
  • severe hypertension (SBP > 180 mmHg and /or DBP > 110 mmHg)
  • acute pericarditis
  • history of stroke
  • major surgical procedure within the previous month.
  • Bleeding is the most common complication encountered during therapy with Tirofiban.
    Most major bleeding occurs at the arterial access site for cardiac catheterization.
  • PRISM Study

TRANSMYOCARDIAL LASER
REVASCULARISATION

  • The transmyocardial laser revascularisation (TMR) is a new method for myocardial revascularisation in patients with severe coronary artery disease not suitable to conventional treatment (medical therapy, coronary angioplasty or bypass surgery).
  • The most TMR procedures have been performed so far with a 800 W CO2 laser.
  • Clinical experiences with other lasers are ongoing.
  • TMR with a new holmium : YAG laser seems safe and appears to be equally to other laser systems in relieving anginal pain and increasing quality of life in patients with severe coronary artery disease.

UNSTABLE ANGINA PECTORIS

Patients with unstable angina are at risk of recurrent and possibly irreversible ischaemia, resulting in progression to myocardial infarction or sudden cardiac death.
Aims of the treatment are not only pain relief but also prevention of recurrent ischaemia or myocardial infarction.
Göbel EJAM et al (Lancet 1995; 346: 1653-1657) published a report in which intravenous Diltiazem was better than intravenous Nitroglycerin at significantly reducing ischaemic events in the first 48h in patients with unstable angina pectoris.
One year follow-up data have shown that the initial benefit obtained by i.v. Diltiazem was preserved during the first year after the hospitalization (Göbel EJAM et al, Eur Heart J 1998; 19: 1208-1213].

VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF)

  • VEGF is an important angiogenic factor that has been reported:
  • to induce migration and proliferation of endothelial cells,
  • to enhance vascular permeability,
  • to modulate thrombogenicity.
  • VEGF may play a role in:
  • tumor growth,
  • wound healing,
  • age-related macular degeneration,
  • rheumatoid arthritis,
  • diabetic retinopathy,
    progression of human coronary atherosclerosis and in recanalization process in obstructive coronary diseases.

VENTRICULAR TACHYCARDIA

  • VT is responsible for the majority of sudden deaths occurring in patients with previous myocardial infarction.
  • Are the patients with more frequent, longer or faster episodes of nonsustained VT at greater risk of sudden death ?
    MUSTT Investigators (Multicenter Unsustained Tachycardia Trial) (Annals of Internal Medicine 1996; 125: 35-39) concluded:
    "The rate, duration and frequency of spontaneous nonsustained ventricular tachycardia in patients with abnormal left ventricular function caused by coronary artery disease cannot be used to make clinical decision".

 

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