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Caso Clinico

Uomo di 65 anni con palpitazioni e


astenia

Prof. Ildo Nicoletti, Medicina Interna PG,


AA. 2004-2005, Primo Semestre
Caso Clinico

• Il paziente giunge in reparto per


– Cardiopalmo e dispnea da sforzo
– Astenia marcata, che aumenta nella giornata
– Dolori ai gruppi muscolari maggiori

• Non reperti di rilievo alla AF


– Modico fumatore (5-6 sigarette) dai 20 ai 35 anni
– Normale assunzione di vino ai pasti
Anamnesi patologica

• Diagnosi endoscopica di ulcera peptica circa 15 anni


or sono risolta dopo un trattamento con anti-H2
• Sporadica assunzione di FANS (classici e Coxib) per
dolori artrosici a carico del ginocchio destro
• Incidente stradale con frattura di clavicola e di tre
coste l’anno scorso
Anamnesi patologica

• Sei mesi fa:


– comparsa improvvisa di cardiopalmo, associato a
sensazione di vertigine ed a scotomi scintillanti
dopo la colazione
– la moglie, infermiera, ha notato un polso celere ed
irregolare e lo ha portato al pronto soccorso
Al Pronto Soccorso

• Conferma di polso aritmico con FC di ca 130 b/min


(115 al polso periferico)
• Anisosfigmia del polso
• Non segni di scompenso cardiaco
• Normale l’esame obiettivo degli altri apparati
• Gli esami di laboratorio ed un ecocardiogramma
eseguiti in urgenza escludono anemizzazione,
disionie, danno miocardico acuto o patologia
valvolare
ECG del paziente

D2

V2
ECG normale
ECG del paziente

D2

V2
ECG in corso di Fibrillazione Atriale

Fibrillazione Atriale

Normale complesso QRS


Atrial Fibrillation

• AF is a common arrhythmia that may occur in paroxysmal and


persistent forms.
• Paroxysmal AF may be seen in normal individuals, particularly
during emotional stress or following surgery, exercise, acute
alcoholic intoxication, or a prominent surge of vagal tone (i.e.,
vasovagal response).
• Persistent AF usually occurs in patients with cardiovascular
disease, most commonly rheumatic heart disease, nonrheumatic
mitral valve disease, hypertensive cardiovascular disease,
chronic lung disease, atrial septal defect, and a variety of
miscellaneous cardiac abnormalities.
• So-called lone AF, which occurs in patients without underlying
heart disease, often represents the tachycardia phase of the
tachycardia-bradycardia syndrome.
Morbidity associated with AF
1. Anxiety secondary to palpitations;
2. Excessive ventricular rate;
this in turn may lead to hypotension, pulmonary congestion, angina
pectoris, and in some patients can produce a tachycardia-mediated
cardiomyopathy;
3. The pause following cessation of AF, which can cause
syncope;
4. Loss of the contribution of atrial contraction to cardiac output,
which may cause fatigue;
in patients with noncompliant ventricles and in mitral stenosis, the
combination of the loss of the atrial contribution to ventricular filling and
the abbreviated filling period due to the rapid ventricular rate in AF can
produce marked hemodynamic instability, resulting in hypotension,
syncope, or heart failure.
5. Systemic embolization, which occurs most commonly in
patients with rheumatic heart disease;

Peters Ns et al. Lancet, 359:593, 2002


Principles of AF management

• Restoration of sinus rhythm


– Electrical cardioversion
– Pharmacological cardioversion
• Maintenance of sinus rhythm
– None or Drug treatment
– Permanent pacing, Radiofrequency ablation, Surgery
• Ventricular rate control
– Calcium-channel blockers, Beta-adrenoceptor
antagonists, Digoxin, Antiarrhytmic drugs
• Reduction of thromboembolic risk
– Warfarin or aspirin

Peters Ns et al. Lancet, 359:593, 2002


Trattamento del paziente

• Un ecocardiogramma trans-esofageo ha
documentato l’assenza di trombi in atrio
• Alla luce di tale dato e della breve durata
della AF il paziente e’ stato trattato con
cardioversione elettrica con ripristino di
un normale ritmo sinusale
• Il paziente e’ stato dimesso senza nessun
trattamento farmacologico aggiuntivo
Decorso

• Dopo 3-4 settimane il paziente lamenta di


nuovo la comparsa di episodi di cardiopalmo
della durata di qualche ora
• Una registrazione ECG dinamica secondo Holter
documenta la presenza di episodi parossistici di
AF di durata variabile da pochi minuti a 4 ore
Nomenclature for Atrial Fibrillation

• Acute:
– an episode of atrial fibrillation, usually within 48 h of its onset
• Paroxysmal:
– intermittent, recurrent, and self-terminating
• Persistent:
– will not self-terminate, but can be effectively cardioverted to sinus
rhythm
• Permanent:
– atrial fibrillation that cannot be terminated by cardioversion, that
can be terminated only for brief intervals, or that lasts longer than
1 year without cardioversion having been attempted
• Chronic:
– implies continuing atrial fibrillation and does not address the
important clinical distinctionbetween persistent and permanent
atrial fibrillation

Peters Ns et al. Lancet, 359:593, 2002


Decorso

• Dopo 3-4 settimane il paziente lamenta di


nuovo la comparsa di episodi di cardiopalmo
della durata di qualche ora
• Una registrazione ECG dinamica secondo Holter
documenta la presenza di episodi parossistici di
AF di durata variabile da pochi minuti a 4 ore
• Per tale ragione il cardiologo che segue il
paziente ha consigliato l’inizio di un trattamento
con anticoagulanti orali in previsione di una
seconda cardioversione. Un secondo cardiologo
ha invece consigliato un trattamento con
farmaci capaci di ridurre la frequenza.
Il paziente vi chiede.....

• E’ giusto fare una seconda


cardioversione o e’ meglio usare
farmaci?
• Ma la terapia anticoagulante e’
necessaria e per quanto?
• Un mio amico usa l’aspirina. Perche’
non posso farlo anch’io?
Nuova cardioversione o controllo
della frequenza?
New Eng J Med. 347, 1825, 2002
Terapia anticoagulante: come e
per quanto tempo?
Risk factors for VTE in patients
with AF

• Data from the Framingham study have shown that


rheumatic heart disease that is complicated by AF is
associated with a 18-fold increase in risk of TE.
• In patients without rheumatic heart disease, atrial
fibrillation raises TE risk by a factor of about six. In
these patients, incidence of ischaemic stroke without
antithrombotic treatment is about 5% per year, but
with large variation. Both TE risk and the
contribution of AF to the causes of ischaemic stroke
increase with age and comorbidity

Peters Ns et al. Lancet, 359:593, 2002


Risk factors for stroke, and indications
for anticoagulation in patients with AF

• Age > 65 years


• Previous history of transient ischaemic
attact or stroke
• History of hypertension
• Diabetes
• Heart failure
• Structural heart disease
• Rheumatic or other significant valvular
heart disease
• Significant left ventricular systolic
dysfunction

Peters Ns et al. Lancet, 359:593, 2002


Atrial Thrombosis in AF

Lip GYH et al. BMJ, 325:1022, 2002


Recommendations for AC for
cardioversion of AF

• For elective cardioversion of AF of > 48 h duration start


warfarin treatment (INR 2-3) three weeks before and
continue for four weeks after cardioversion
• In urgent and emergency cardioversion administer iv
Heparin followed by warfarin
• Treat atrial flutter similarly
• No AC treatment is required for SV tachycardia of AF of
< 48 h duration
• Continue AC in patients with multiple risk factors or those
at high risk of recurrent TE

ACCP Consensus Conference on AT Therapy, 2001


Warfarin o Aspirina?
Meta-analysis of trials with warfarin
for prevention of TE in AF

Lip GYH et al. BMJ, 325:1022, 2002


Meta-analysis of trials with Aspirin
for prevention of TE in AF

Lip GYH et al. BMJ, 325:1022, 2002


Practical guidelines for anti-
thrombotic therapy in non-valvar AF

Lip GYH et al. BMJ, 325:1022, 2002


Practical guidelines for anti-
thrombotic therapy in non-valvar AF

Lip GYH et al. BMJ, 325:1022, 2002


LFV is a good predictor of Stroke
risk in AF

Lip GYH et al. BMJ, 325:1022, 2002


Nell’ ultimo mese....

• Il paziente e’ in trattamento con verapamil ed


aspirina
• Continua a lamentare Cardiopalmo ed e’
comparsa dispnea da sforzo
• Lamenta anche:
– Astenia marcata, che aumenta nella giornata
– Dolori ai gruppi muscolari maggiori
Il medico di base ha consigliato il
ricovero......

...... sospettando un ipertiroidismo


Principali manifestazioni cliniche
dell’Ipertiroidismo

• Sintomi • Segni
– Astenia e debolezza muscolare – Tachicardia sinusale
– Mialgie – Aritmie
– Irritabilita’ – Cute calda e sudata
– Intolleranza al caldo e diaforesi – Aumento della pressione
– Iperattivita’ differenziale
– Cardiopalmo – Retrazione della palpebra e “lag lid”
– Aumento appetito – Iperreflessia
– Riduzione del peso corporeo – Dolorabilita’ muscolare
– Alterazioni mestruali e/o della – Tremori
libido – Onicolisi
– In casi particolari disturbi cutanei – In casi particolari variazioni di
ed oculari volume della tiroide, oftalmopatia,
dermopatia
Tests for thyroid dysfunctions

Thyroid Physiology TESTS THAT ASSESS METABOLIC


IMPACT OF THYROID HORMONES

• Serum cholesterol
• BMR

TESTS THAT ASSESS PITUITARY


IMPACT OF THYROID HORMONES
• Serum TSH
IODINE • TRH test
UPTAKE
TESTS RELATED TO CONCENTRATION OF
THYROID HORMONES IN THE BLOOD
• Serum T3 and T4
• Serum fT3 and fT4
• Serum rT3
OTHER TESTS
• Serum TbG
• TS Immunoglobulins
• Anti TPO and TG antibodies
Valutazione dei vari tests di laboratorio
nella diagnostica delle disfunzioni tiroidee

• T4 e/o T3 totali: da non utilizzare. Specificità e valore predittivo


positivo troppo bassi
• Tiroxina libera (free-T4): specificità discreta. Rimangono alcuni
problemi metodologici (gold standard “equilibrium dialysis”) che
portano ad ampie variazioni inter-laboratorio. Non identifica la
“T3-toxicosis” e puo’ dare falsi positivi nella “sick euthyroid
syndrome”
• Tri-iodotironina libera (free-T3): non utilizzabile come test
unico per sensibilità troppo bassa.
• TSH sensitive o supersensitive: buone sensibilità (89-95%) e
specificità (90-96%). I falsi positivi sono spesso legati a farmaci
(corticosteroidi)
Relationships between fT4 and s-TSH
levels in Thyroidal Disorders

Scientific American Medicine , 2003


s-TSH as Screening Test for
Hyperthyroidism

“... sensitive TSH measurements are the single


best screening test for hyperthyroidism.”

AACE Clinical Practice Guidelines for the


Evaluation and Treatment of Hypertiroidism and
Hypothyroidism, Washington, DC, 2002
Determinazione di fT4 e s-TSH nel
paziente

• Free T4: 1.9 ng/dl V.N. 0.9-2.0


• s-TSH: <0.01 µg/dl V.N. 0.5-5.0

Come interpretare tale incongruenza?


s-TSH pittfalls

• TSH is not reliable in cases of suspected pituitary


disease (FT4 is recommended).
• TSH may be an unreliable indicator of thyroid status
in patients with acute severe nonthyroidal illness
(e.g., CCU, ICU, acute severe psychiatric illness). In
these cases FT4 is recommended.
• Within 3 months of a change in therapy for
hyperthyroidism TSH may not reflect the clinical
status. In these cases a FT4 test (or equivalent) or
FT3 test (or equivalent) is recommended.
Differential diagnosis of low s-TSH

Hanna FHW, Lazarus JH and Scanlon MF, BMJ, 1999


Subclinical Hyperthyroidism

• The combination of an undetectable serum thyrotropin


concentration, as measured by an assay with a threshold of
detection that is 0.1 mU per liter or less, and normal serum
triiodothyronine and thyroxine concentrations (usually at the
upper end of the normal range) is known as subclinical
hyperthyroidism.
• When the lower limit of TSH is less than 0.4 mIU/L, 3.2% of
the population is defined as having subclinical HT. If the
diagnosis is limited to only those with TSH lower than 0.1
mIU/L the prevalence decreases to 0.7%.
• Subclinical HT is common in individuals treated with l-
thyroxine being present in 14% to 21% of such patients.

Toft AD, N Engl J Med, 2001


Natural history of subclinical
hyperthyroidism

Toft AD, N Engl J Med, 2001


Does Subclinical Hyperthyroidism
have adverse clinical effects?
Atrial fibrillation in subclinical
hyperthyroidism

TSH <0.1 TSH 0.1-0.5 TSH >0.5


Serum TSH mU/L

Sawin et al, N Eng J Med, 331:1249, 1994


Subclinical hyperthyroidism and
cardiovascular diseases

• 1191 old patients (>60 yrs) followed from 1988 to


1999 in Birmingham, UK
• Thyroid function tests (sTSH, fT4 e fT3) were
measured in 1988
• Vital status was recorded on June 1 1999:
– phone call of survived patients
– ascertainment of date and cause of death for
those who had died through the records of UK
NHS Central Register

Parle et al, Lancet, 358:861, 2001


Subclinical hyperthyroidism and
cardiovascular diseases
• During follow-up, 509 of 1191 people died, the expected number
of deaths being 496 (standardised mortality ratio [SMR] 1.0, 95%
CI 0.9–1.1).
• Mortality from all causes was significantly increased at 2 (SMR
2.1), 3 (2.1), 4 (1.7), and 5 (1.8) years after first measurement
in those with low serum thyrotropin (n=71).
• Increases in mortality from all causes in years 2–5 were higher in
patients with low serum thyrotropin than in the rest of the cohort
(hazard ratios for years 2, 3, 4, and 5 were 2.1, 2.2, 1.8, and 1.8,
respectively). This result reflects an increase in mortality from
circulatory diseases (hazard ratios at years 2, 3, 4, and 5 were
2.3, 2.6, 2.3, 2.3), and specifically from cardiovascular diseases
(hazard ratios at years 2, 3, 4, and 5 were 3.3, 3.0, 2.3, 2.2).

Parle et al, Lancet, 358:861, 2001


Kaplan-Meier survival curves according
to serum TSH levels

Survival for CV diseases(%)


Overall survival (%)

Years of follow-up Years of follow-up

Parle et al, Lancet, 358:861, 2001


Ma il paziente ha un
ipertiroidismo?
E se e’ ipertiroideo, qual’e’ la
causa?
Diagnosis of Hyperthyroidism
Sensitive TSH Assay plus free-T4

Subnormal

/=Free T4

Borderline Suspect
 Free T3 T3 Toxicosis
thyroid status Perform RAIU &
SCAN
(the majority of T3 toxicosis
TSH after
are due to iperactive
 Free T3 Pituitary
TRH Test thyroid nodules)
Hypothyroidism

Sick Euthyroid
Syndrome
Determinazione di fT4, fT3 e s-TSH
nel paziente

• Free T4: 1.9 ng/dl V.N. 0.9-2.0


• s-TSH: <0.01 µg/dl V.N. 0.5-5.0
• Free T3: 2.5 ng/dl V.N. 0.2-0.6

La determinazione della free-T3 risolve la apparente


incongruenza: il paziente ha una “T3 tireotossicosi”
Main causes of Hyperthyroidism

Franklin JA, New Eng J Med 1998


Thyroid autonomy and TSH

T4-T3

Scientific American Medicine , 2003


Scintigrafia tiroidea con 131I nel
paziente

Tiroide normale Tiroide del paziente


Caratteri distintivi della T3-tossicosi
• Prevale nei pazienti sopra i 60 anni ed e’ quasi
sempre sostenuta da noduli autonomi
• Gli apparati maggiormente coinvolti sono:
– Cardiovascolare:
• Fibrillazione atriale e TPSV
• Scompenso congestizio
• Angina ed infarto
– Neuromuscolare:
• Astenia e debolezza
• Mialgie ed Atrofia muscolare (quadricipite)
• Apatia, depressione, deterioramento cognitivo
– Gastroenterico:
• Anoressia, stipsi e perdita ponderale
Diagnosi finale:

• Fibrillazione Atriale in paziente


con Gozzo Nodulare (M. di
Plummer) e T3-tireotossicosi
Letteratura di approfondimento:

• Editorial: Management of AF - Radical reform or modest


modification? N Engl J Med 347:1883, 2002
• Peters NS et al. AF: strategies to control, combat and
cure. Lancet 359:593, 2002
• Lip GYH et al. Antithrombotic therapy for AF. BMJ
325:1022, 2002
• Hegedus L: The thyroid nodule. N Engl J Med 351:1764,
2004
• Surks MI et al. Subclinical thyroid disease: scientific
review and guidelines for diagnosis and management.
JAMA 291:228, 2004