Autonomic cardiovascular control and cardiac arrhythmia in two pregnant women with hypertrophic cardiomyopathy: Insights from ICD monitoring.

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RevPortCardiol.2018;37(4):351.e1---351.e4

www.revportcardiol.org

Revista

Portuguesa

de

Cardiologia

Portuguese

Journal

of

Cardiology

CASE

REPORT

Autonomic

cardiovascular

control

and

cardiac

arrhythmia

in

two

pregnant

women

with

hypertrophic

cardiomyopathy:

Insights

from

ICD

monitoring

Pietro

Francia

∗

,

Carmen

Adduci,

Beatrice

Musumeci,

Lorenzo

Semprini,

Francesca

Palano,

Luigi

Zezza,

Massimo

Volpe,

Camillo

Autore

DepartmentofClinicalandMolecularMedicine,St.AndreaHospital,SapienzaUniversity,Rome,Italy

Received19December2016;accepted11September2017 Availableonline17April2018

KEYWORDS Hypertrophic cardiomyopathy; Pregnancy; Implantable cardioverter deﬁbrillator;

Heartratevariability; Ventricular

arrhythmia

Abstract In women with hypertrophic cardiomyopathy (HCM), pregnancy prompts major

changes inhemodynamicandcardiacautonomicfunction thatmay precipitateheart failure (HF)orincreasetheriskofcardiacarrhythmia.

Wereporttheclinicalfollow-upoftwopatientswithnon-obstructiveHCMimplantedwitha cardioverterdeﬁbrillator(ICD)allowingforcontinuousanalysisofheartrate(HR),heartrate variability(HRV)andcardiacarrhythmiathroughouttheentirecourseofpregnancy.

BothpatientsexperiencedincreasedHRanddecreasedHRVfromtheearlystagesof preg-nancy, whichpersisteduntil delivery.Prematureventricularcontractions(PVCs)andrunsof non-sustainedventriculartachycardia(NSVT)reachedapeakinthesecondandthirdtrimesters, concurrentwithsympathetichyperactivity.InonepatientwithbaselineNYHAclassIIHF symp-toms,increasedPVCsandNSVTwereconsistentwiththedeterioration ofHF,supportingthe decisiontobringthedeliveryforward.Whilebothpatientsexperiencedapersistentincrease in sympathetic tone and ventricular ectopic activity, no life-threatening arrhythmias were documented.

Duringpregnancy,patientswithhypertrophiccardiomyopathydevelopprogressive neuroauto-nomicimbalance,promptinganincreaseinnon-sustainedventriculararrhythmia.Thisenhanced arrhythmiaburdenwarrantsclosefollow-upandrhythmassessmentduringthethirdtrimester, especially inwomen who have heart failuresymptoms before pregnancy. Implantable car-dioverter deﬁbrillatorsprovideacontinuousanalysisofheartratevariabilityandarrhythmia burdenthatsupportstherapeuticdecision-makingduringfollow-up.

∗_{Corresponding}_author.

E-mailaddress:pietro.francia@uniroma1.it(P.Francia).

https://doi.org/10.1016/j.repc.2017.09.019

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351.e2 P.Franciaetal. PALAVRAS-CHAVE Miocardiopatia hipertróﬁca; Gravidez; Cardioversor-desﬁbrilhador implantável; Variabilidadeda frequênciacardíaca; Arritmiaventricular

Controlecardiovascularautonómicoearritmiacardíacaemduasgestantes

commiocardiopatiahipertróﬁca:observac¸õespormeiodomonitoramentocomCDI

Resumo Em mulheres com miocardiopatia hipertróﬁca, a gravidez aumenta as variac¸ões

hemodinâmicas e as alterações da função autonómica cardíaca que podem provocar insu-ficiênciacardíaca ou aumentaro risco dearritmia. Reportamoso acompanhamento clínico de duaspacientescom miocardiopatia hipertróficanão obstrutiva, ambas implantadascom cardioversor-desfibrilhador(CID).A monitoraçãocomCIDpermiteaanálisecontínuada fre-quênciacardíaca,davariabilidadedafrequênciacardíaca(VFC)edaarritmiadurantetodaa gravidez.AsduaspacientesmanifestaramaumentosdaFCediminuiçõesdaVFCdesdeoinício dagravidezatéaoparto.Observou-se umpicodefrequênciadeextrassístolesventriculares (EV)edetaquicardiasventricularesnãosustentadas(TVNS)nosegundoeterceirotrimestres dagestação,emcorrespondênciadahiperatividadesimpática.Numadaspacientescomclasse funcionalNYHAII,antesdagravidez,oaumentode EVedeTVNScontemporaneamente ao agravamentodainsuficiênciacardíacalevouàdecisãodeanteciparoparto.Asduaspacientes demonstraramumaumentopersistentedaatividadesimpáticaedaatividadeectópica ventric-ular,nãoexistiramcasosdearritmiasventricularesmalignas.Duranteagravidezaspacientes commiocardiopatia hipertróficadesenvolvem um progressivodesequilíbrio autonómico que causaumaumentodasarritmiasventricularesnãosustentadas.Oaumentodoriscoarrítmico necessitade um constanteefrequente controleclínico edo ritmocardíaco duranteo ter-ceirotrimestre,especialmenteemmulherescomsintomasdeinsuficiênciacardíacaantesda gravidez.Ocardioversor-desfibrilhadorimplantávelforneceumaanálisecontinuada variabili-dadedafrequênciacardíacaedasarritmiasquepodemapoiarasdecisõesterapêuticasdurante agravidez.

Background

Maternaldeathisrareinpregnantwomenwithhypertrophic cardiomyopathy(HCM).However,thedeteriorationof clini-calconditionsmayoccurinasmallbutsigniﬁcantproportion ofpatients1_._Pregnancy_prompts_major_changes_in

hemody-namicandcardiacautonomicfunctionthatmayprecipitate heart failure or increase the risk of cardiac arrhythmia. Thispaperreportstheclinicalanddevicefollow-upoftwo patients with non-obstructive HCM implanted with a car-dioverterdeﬁbrillator (ICD),thereby providingcontinuous analysisofheartrate(HR),heartratevariability(HRV)and cardiac arrhythmia throughout the entire course of preg-nancy.

Case

report

Patient A had been diagnosed with HCM at the age of 14and implantedwith asingle-chamber ICD(Maximo VR, Medtronic) at the age of 22 based on massive left ven-tricular(LV)hypertrophy(>30mmmaximalwallthickness), non-sustainedventricular tachycardia(NSVT)anda family historyof unexplained sudden deathin a ﬁrst-degree rel-ative<50 yearsof age2,3_._She _underwent_a _life-saving_ICD

intervention for ventricular ﬁbrillation (VF) at the age of 26.

Atweek1ofpregnancyshewas30yearsold,hadNYHA classIIsymptomsandwasontreatmentwithatenolol50mg daily.Duringpregnancy,sheunderwentroutineclinicaland

ICDfollow-upvisitseverytwotothreemonths.AteachICD interrogation, HR trends, HRV (expressed as SDNN, stan-dard deviation of normal-to-normal RR intervals), single premature ventricularcontractions (PVCs),series of PVCs (2---4beats),runs ofNSVT(>4beats)andatrial ﬁbrillation (AF)episodeswererecorded.

Data retrieved from the ICD showed increased HR and decreased SDNN from the early stages of pregnancy (week4),withapeakandplateauinthesecondandthird trimesters (Figure, panel A). She experienced eight runs of NSVT between week 12 and week 30, together with a substantial increaseof single PVCs(from 280 to2500 per day onaverage) andseriesofPVCs(from190 to1500 per day on average) from week 18 that persisted until deliv-ery (Figure, panelA).The patientdidnot experienceany episodes of AF. Compared to baseline, during the third trimester, patientA experiencedprogressive worseningof heartfailuresymptoms(transitionfromNYHAclassIItoIII), increased pulmonary artery pressure(PAP) asassessed by Dopplerechocardiography(from30mmHgto45mmHg)and increasedventricularectopicactivity,asrecordedbytheICD (Figure,panelA).Asaresult,cesareandeliverywas sched-uled at week 30and thepre-term infantwastemporarily admitted to the neonatal intensive care unit. Drug ther-apydidnotchangethroughoutfollow-up.AtICDfollow-up (12weeksafterdelivery),HR,SDNNandPVCswerefoundto beatpre-pregnancylevels.

Patient Bhad been diagnosed with HCM at the age of 12andimplantedwithaprimarypreventionsingle-chamber ICD (Entrust VR, Medtronic) at the age of 30 based on

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Neuro-autonomicdriveandarrhythmiainHCMduringpregnancy 351.e3

A

2400 PVC or PVC r uns per da y PVC or PVC r uns per da y 2000 1600 1200 800 400 0 2400 > 120 Average HR (bpm) Patient activity hours/day Heaty rate variability (ms) Day Night Average HR (bpm) Patient activity hours/day Heaty rate variability (ms) Day Night > 8 > 200 160 120 80 < 40 Aug 2010 Single PVC/day Run 2-4 PVC/day Single PVC/day Run 2-4 PVC/day

First trimester Second trimester Third trimester

Oct 2010 Dec 2010 Feb 2011 Apr 2011 Jun 2011 Aug 2011 6 4 2 0 100 80 60 < 40 2000 1600 1200 800 400 0 > 120 100 80 60 < 40 > 8 > 200 160 120 80 < 40

Nov 2013 Jan 2014 Mar 2014 May 2014 Jul 2014 Sep 2014 Nov 2014 6

4 2 0

B

Figure1 PVC,PVCseries,HR,dailyactivity(hours)andHRV(SDNN)throughouttheentirecourseofpregnancyasretrievedfrom theICDmemoryinpatientA(panelA)andpatientB(panelB).

ThenumberofPVCsisshownatthemidpointbetweentwocloseclinicalevaluationsandICDfollow-upvisits.

PVC,prematureventricularcontraction;HR,heartrate;HRV,heartratevariability;SDNN,standarddeviationofnormal-to-normal RRintervals.

massiveLVhypertrophyandNSVT2_._She_never_experienced

ICDinterventions.

At week 1 of pregnancy, Patient B was 37 years old, asymptomatic,andonatenolol,25mgdaily.

She underwentroutineclinical andICD follow-upvisits throughoutpregnancy(everytwotothreemonths).Ateach ICD interrogation, HR trends, HRV, single PVCs, series of

PVCs,runsofNSVTandatrialﬁbrillation(AF)episodeswere retrievedfromtheICDmemory.

Duringpregnancy, data retrievedfrom the ICDshowed increasedHRanddecreasedSDNNfromweek4withapeak andplateauinthethirdtrimester(Figure,panelB).Patient BexperiencedanincreaseinsinglePVCs(from34to1400per dayonaverage)andseriesofPVCs(from70to500perday

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351.e4 P.Franciaetal. onaverage)fromweek 16untildelivery (Figure, panelB).

Duringthethirdtrimester,shedidnotexperienceany dete-riorationofheartfailuresymptomsorAFepisodes,andPAP remainedwithinthenormalrange(max.26mmHg).Atenolol wasnotup-titratedduringfollow-up.Thepatientunderwent uncomplicatedcesareandeliveryatweek34after oligohy-dramnios.Thebabywasborningoodhealth.Duringroutine ICDfollow-up10 weeksafterdelivery,HR,SDNNand ven-tricularectopicactivitywerefoundtobeatpre-pregnancy levels.

Discussion

In healthy women, pregnancyis associated with hemody-namic and cardiac autonomic changes4_. _Indeed, _HR _rises

asacompensatory response toreducedsystemic vascular resistanceandHRV decreases duetoa shiftin autonomic balancetowardssympathetichyperactivity5_._The_extent_to

whichthisoccursinpregnantwomenwithHCMandwhether itmayaffect theriskof cardiacarrhythmiaandprognosis is currently unknown. For the ﬁrst time, we used an ICD forcontinuousbeat-to-beatanalysisofHR,HRVandcardiac arrhythmiathroughouttheentirecourseofpregnancyintwo high-riskHCMpatients.

HRVanalysisshowedapersistentriseinsympathetictone earlyinpregnancy.Ontheonehand,ﬂuctuationsinplasma estrogenandprogesteronemayexplaintheincreased sym-pathetic outﬂow that, in turn, triggers PVCs and NSVT as a result of beta-adrenergic stimulation of the hyper-trophic myocardium. On the other hand, the increase in ventricularectopicactivitymayoccurasaresultof disease-relatedfailuretocompensatefor expanded blood volume and tachycardia, particularly in the context of massive LV hypertrophy and diastolic dysfunction. Irrespective of whetherenhancedectopicactivityisprimaryorsecondary inorigin,cardiacrhythmassessmentisreasonable evenin the early stages of pregnancy in HCM patients. Nonethe-less, sympathetichyperactivity, PVCs and NSVTshowed a peakin the second andthird trimesters,concurrent with maximumvolumeoverload, HR,cardiacoutputand circu-latingcatecholamines.Thismarkedincreaseinventricular arrhythmiawasconsistentwithdeteriorationofheart fail-uresymptomsandsupportedthedecisiontoanticipatethe deliveryin patientA. Accordingly,closeclinical follow-up includingrhythmassessment iswarrantedin HCMpatients during the third trimester, especially in women who are symptomaticbeforepregnancy.Heartfailuresymptomsand cardiac arrhythmia may indicate the need for cesarean and/orearlydelivery.

Finally, while both patients experienced a persistent increaseinventricularectopicactivity,nolife-threatening arrhythmiawasdocumented.Thisisconsistentwithprevious studiesthathaveshownthatsustainedventricular arrhyth-mia isuncommon in pregnantwomen withHCM,and that PVCsandNSVTdonotpredictpersetheriskofdeath1,6,7_.

Conclusions

During pregnancy, patients with hypertrophic cardiomy-opathy develop progressive neuroautonomic imbalance promptinganincreaseinnon-sustainedventricular arrhyth-mia. This enhanced arrhythmia burden warrants close follow-upandrhythmassessmentduringthethirdtrimester, especially in women who have heart failure symptoms before pregnancy. Implantable cardioverter deﬁbrillators provide a continuous analysis of heart rate variability andarrhythmiaburdenthatsupportstherapeutic decision-makingduringfollow-up.

Conﬂict

of

interest

Dr. Pietro Francia served as consultant and received speaker’sfeesfromBostonScientiﬁc.

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