Cc rr REVIEW European Society oi10.1093/ehjcvpipyx019 ot cnlon Hypertension and cardiac arrhythmias: executive summary of a consensus document from the European Heart Rhythm Association (EHRA) and ESC Council on Hypertension, endorsed by the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulacion Cardiaca y Electrofisiologia (SOLEACE) Gregory Y. H. Lip"”, Antonio Coca™*, Thomas Kahan“, Giuseppe Boriani®, Antonis S. Manolis’, Michael Hecht Olsen’, Ali Oto’, Tatjana S. Potpara'®, Jan Steffel"’, Francisco Marin'?, Marcio Jansen de Oliveira Figueiredo", Giovanni de Simone", Wendy S. Tzou'®, Chern En Chiang", and Bryan Williams’? Reviewers: Gheorghe-Andrei Dan (Romania), Bulent Gorenek (Turkey), Laurent Fauchier (France), Irina Savelieva (UK), Robert Hatala (Slovakia), Isabelle van Gelder (The Netherlands), Jana Brguljan-Hitij (Slovenia), Serap Erdine (Turkey), Dragan Lovié (Serbia), Young-Hoon Kim (Republic of Korea), Jorge Salinas-Arce (Pert), and Michael Field (USA). ‘ottuteof Cardone cence Unversity of 8 Uk: "Deparment of Cn Medina, bore Theomboss Reserch Unt Aalborg tute of Cardo Since, Unversty Clee Londen, UR cee 25 Ap 2017 reve 12 Mey 2017; edit Secs 22 Mey 207: cated 23 May 2017: erie pubshaeadfp 20 je 2017 * Comerpondng shor. Tet 4992275759, Fal aroexeieber bite on ba the European Sxety of Carino Alri reed. © The Author 207. F 1202 soquis00q ¢z vo 1son8 faq s9atsee/sez/heyetoueHdnolyanuoo cho onuopene} sci WOH PepEOHNG236 GYH Lp etal Hypertension (HTN) is a common cardiovascular risk factor leading to heart fallure (HF), coronary artery disease (CAD), stroke, periph- eral artery disease and chronic renal failure, Hypertensive heart dsease can manifest as many types of carlac arrhythmias, most com- ‘monly being atrial fibration (AF). Both supraventricular and ventricular arrhythmias may occur in HTN patients, especially in those with left ventricular hypertrophy (LVH), CAD, or HF. In addition, high doses of thazide diuretics commonly used to treat HTN, may result in clectroiyte abnormalities (eg, hypokalaemia, hypomagnesaemia), contributing further to arrhythmias, while effective blood pressure con- trol may prevent the development ofthe arrhythmias such as AF In recognizing this close relationship between HTN and arrhythmias, the European Heart Rhythm Association (EHRA) and the European Society of Cardiology (ESC) Council on Hypertension convened a Task Force, with representation from the Heart Rhythm Society (HRS), ‘Asia-Pacific Heart Rhythm Society (APHIS), and Sociedad Latinoamericana de Estimulacién Cardiaca y Electrofisiologla (SOLEACE), with the remit of comprehensively reviewing the available evidence and publishing a joint consensus document on HTN and cardiac arrhyth- rmias, nd providing up-to-date consensus recommendations for use in clinical practice. The ultimate judgment on the care of a specific patient must be made by the healthcare provider and the patient in light of ll individual factors presented, This is an executive summary ibished by EHRA in EP-Europace Hypertension * Avil fbrilation + Arrhythmias * Left ventricular hypertrophy data exist In controversial areas, or with respect to issues without evidence other than usual cnical practice, consensus was achieved by agreement ofthe expert panel after thorough deliberation In contrast to guidelines, we opted for an easier and user- ‘Fiendly system of ranking using coloured hearts’ that should allow physicians to easly assess the current status of the evidence and consequent guidance (Table 1). This EHRA grading of consensus statements does not have separate defntions ofthe level of evi- dence. This categorization, used for consensus statements, must not be considered as directly similar to that used for official soci ety guideline recommendations, which apply a classification (Class Hl and level of evidence (A,B, and C) to recommendations used in oficial guidelines Thus, a green heart indicates a ‘should do this’ consensus state- ment or indicated treatment or procedure that is based on a last fone randomized trial, or is supported by strong observational evi= dence that is beneficial and effecve, A yellow heart indicates gen- eral agreement andlor scientific evidence favouring a ‘may do ths! statement oF the usefulnesseficacy of a treatment or procedure. Preamble Hypertension (HTN) i a common cardiovascular risk factor (CVRF) and underies many cardiovascular (CV) conditions, including heart failure (HF), coronary artery disease (CAD), stroke, and chronic renal failure (CRF). Hypertensive heart disease may manifest as var ‘ous cardiac arrhythmias, mast commonly atrial brilation (AF). Both ‘AF and HTN individually contribute to an increased stroke risk, which is further accentuated when both are present in combination Both supraventricular arrhythmias and ventricular arthythmias may ‘occurin the HT patients, especially when associated with lef ventric lar hypertrophy (LVH) or HF. In addtion, some ofthe anthyperten- sive drugs commonly used to reduce blood pressure (BP), such as thiazide duretcs, may rest in electro} abnormalities (eg. hypo- alaemia, hypomagnesemia), further contributing to arrhythmias, Whereas effective control of BP may prevent the development ofthe arrhythmias such as AF. In recognizing this close relationship between HTN and arrhyth- rmias, the European Heart Rhythm Assocation (EHRA) and the European Society of Cardiology (ESC) Councilon Hypertension con- : A yellow heart symbol may be supported by randomized trials based vened a Task Force, with representation from the Heart Rhythm on a small number of patients or which is not widely applicable. Society (HRS), Asa-Pactic Heart Rhythm Society (APHRS), and: Treatment strategies for which there is scientific evidence of poten- Sociedad Latinoamericana de Estimulacién Cardiacay tial harm and should not be used (do not do this) are indicated by a Electrofsiologia (SOLEACE), with the remit of comprehensively: radheart reviewing the avaiable evidence and publishing a joint consensus document on HTN and carte arrhythmias, and providing up-to- date consensus recommendations for use in clinieal practice The ult= ‘mate judgment on the care ofa specific patient must be made by the healthcare provider and the patient in ight of all individual factors presented. This isan executive summary ofthe full document co- published by EHRA in EP-Europace. Pathogenesis of arrhythmias in hypertension—a brief overview Haemodynamic changes, neuroendocrine factors, arial and venti larsuctural remodeling (e. myocardial Soros), and a proarryth- mogeric electrophysoiogc phenotype of a hypervophied left ventrile, and prolonged QTe interval al contribute tothe complex pathophysiology ofarchytimogenest in HTN! Atrial frilton is the most frequent anthythmia in hypertensive patients and HTNis the mest prevalent co-morbidity inpatients with [AF.Poor BP contal seems ta worsen outcomesin AF via ef vertric- ar diastole dysfunction {where associated HF is present, thsi refered to as HF wth preserved ejection fraction (HFpEF et atria Evidence review “This document wa prepared by the Task Force with representation from EHR, HRS, APHRS, and SOLAECE and peer-reviewed by off ial external reviewers representing EHRA, HRS, APHRS, and SOLAECE. Their members made a detailed Iterature review, weigh- Ingthe strength of evidence for or agunsta specific treatment or pro- cedure, and including estimates of expected health outcomes where wopeoe)rsdiy woy popeojunod +202 soquie20q ¢z vo 1sen8 fq soapsee/sezibree(onserlyorwon‘énoHypertension and cardia arthythmias 237 ‘overload and remodeling, Atrial frilation is also related to the cir cadian rhythm of BP whereby a blunted nocturnal fall increases the ‘occurrence of AF, perhaps due tothe sustainability ofhigh BP and the resuitant hemodynamic burden on the left atrium? Myocardial changes induced by HT have been described in detail Mechanical overload due to high BP may induce an ‘Table | Scientific rationale of recommendations” Definitions where related toa Consensus Symbol ‘treatment or procedure statement “Should do thi y May do wie ~ === = y ee a [SSS SS abnormal expression ofion channels andor junctional complexes, such as connexin 40 and connexin 43, which can enhance myocar- dium vulnerability by triggering focal ectopic and re-entry activity." ‘Activation of the renin-angiotensin-aldosterone system (RAAS) i strongly implicated in the development of AF. AF may also induce microvascular dysfunction in the ventricles® Angiotensin Il pro: motes fibrosis via AT1 receptors by increasing the synthesis of TGF-betat in the atria and ventricles, as well as the release of growth factors and inflammation mediators such as IL-6* Structural remodeling results in dsruption of the myocardal ell, bundles andheterogeneity in intra-atral conduction creates sub- strate for multiple reentrant cicuts which hes perpetuate the triggered AF. Aldosterone-induced oxidative stress and infarmma- tion is an ‘add on’ effect of RAAS favouring atrial structural and electrical remodeling. Moreover arial fbrosishas been shown to create a thrombogenic mileu which may underlie thromboem- bolic events even in the absence of AR* Left ventricular hypertrophy i ao the major determinant of the development of ventricular arrhythmias and sudden eardac death {8CD) in hypertensive patients. Activation ofthe sympathetic nerv- cus ayntem and RAAS are important components ofthe pathophysi- logy and development of LVH (Fgure 1). Sympathetic actvation ‘may trigger ventricular arrhythmias? Prolongation and dispersion of repolarazation is another feature of the pro-arhythmogenic impact of LH." Nocturnal arrhythmias ineuding sinus arrest, second- degree AV block, ventricular premature beats (VPBs) and non-sus- tained ventrcuartachyeara (NSVT have been eeported in up to 50% of sleep apnoea patients Sleep apna is known to predispose to the development of AF About 50% of sleep apnoea patients are hypertensive” and about 30% of hypertensive patients aso have ‘Acthe cellular level, structural remodeling induced by HT fs asso cated with impaired eall-o-cell communication at gap junctions, and 's the bass of nor-homogenous impulse propagation and re-entrant Figure 1 Mechanisms of arrhythmias in hypertension LA, left atrium: LVH, lft ventricular hypertrophy; RAS, reninangitensinaldosterone system, wopeoeyrsdiy wou popeojunog 1202 s0quis00q ¢z vo 1son8 fa soarsee/sezitreerouerdnlyanuco‘éno238 GYH Lp etal ventricular arrhythmias?" Left ventricular hypertrophy is also a source of myocardial ischaemia due to the mismatch of oxygen sup- ply and demand, which may trigger of ventricular arrhythmias and SCD in some cases," Supraventricular arrhythmias Supraventricular ectopics Studies show that supraventricular ectopics (SVPBs) and VPBs ‘occur frequently in hypertensive patients with LVH.”” A non- dipping profile (nocturnal BP reduction <10% vs. diurnal BP) and Increased nocturnal BP are markers of more advanced target corgan damage: thus, non-dipping is commonly associated with arrhythmias.® Recovery from exercise may be another triggering factor for SSVPBs and the subsequent occurrence of AF." Patients with excessive SVPBs and LVH have a greater risk of developing AF, Which is associated with increased age, SBP, and N-terminal pro brain natriuretic peptide (NT-proBNP) levels.” Interestingly, stroke was commonly the fist clinical presentation, beyond ma fest AF in these study subjects. Even short runs of 20-50 SVPBs are associated with AF or some cryptogenic stroke events and Ischaemic stroke." ‘Consensus statements References © Paton with requent SVPBs and LVHL » have ahigher probability of AE, and pro- longed ECG monitoring to detect AF may be used poe © Cafeine) and opting BP control. expecially patients with LVH ECG, decrocaiopam, Atrial fibrillation Due to its high prevalence in the general population, HTN isthe ‘most significant populaton-attrbutablersk for AF and has been est- ‘mated to be responsible for 14% ofall AF cases HTN was present in >70% of AF patients in epidemiological studies” and recent AF real-world registries" and in 49-90% of patients in randomized AF trials? An increased AF risk was also reported in individuals with Upper normal BP2* Hypertension has been identified as an independent risk factor for incident AF?” or AF progression." AF-related stroke, silent lacunar infarcts and mortality.” and bleeding. complications of coral anticoagulant therapy in AF patients,” and a contributor to an increased isk of poor quality of treatment with vitamin K antagonists, as predicted by the SAMe-TT,Ry score.”" AF may be asymptomatic in up to 35% of patients (including those with symp- tomatic AF episodes)” particularly in patients with less comor- bidity (eg. with HTN only).?? ‘Consensus statements © AF shouldbe considered asa manifesta ne ‘ion of hypertensive heart disease and ETN management shoul be opsinizod * Given that stroke prevention central » to the management of AF patients, the 80-85 bpm may be used as a guide to investigate for occutt HF symptoms by cnical examination or determination of biomarkers (such as BNP) or by echocardiogram, or searching for sesociated comorbidities, such as arrhythmias (eg. AF and aril fut ter), anaemia, hyperthyroidism, and sepsis." In AF, rate control should intaly aim for a HR <110 bpm, with stricter rate control if symptomatic oF LV function deteriorates.” The beneficial effects of beta-blockers on outcomes may be less apparentin patents with AF and reduced LY systolic function *® References “Consensus statements * Sinus node and AV conduction ctr ances (pasculry in pasens with LVH) may eccurin HTN paints asa consequence of sleep apra,and sleep ordered breathing more common In these paints. Thus, HTN pasens should be sstezre fr these conditions © Conduction delays occur both atthe suvaland ventiulaelevel in HTN pation, parcularty those wth LYH, leading to AF or SCO. LBBB in HTN, especaly with LVH, denis pater, at inreased cardiovascular rik. Thus, HIN patents shouldbe assessed for these condone © An inrecsed resting hear rate (780-85 bpm), portend an averse prognosis, not only in patients with CAD and HE butalsoin HTN pavens. Routine HR. lowering using beta blockers or other agen may be considered in HTN subjects uncomplicated by other comorbidities (eg impaired LY faneton), ~~ Proposal for a standardized ‘workup’ Jn most patents with HTN and suspected arrhythmias, al efforts should be made to obtain a dagnoss by documenting the arty, Regular SVTs, including. atrioventricular nodal reentrant tachycardia, avioventricular re-entranttachyearda arial utter, and focal atral tachycardia may ead to severe symptoms inpatient with HIN, in whom curative treatment with catheter ablation as well ‘medical therapy may have high success and low-complication rates.” “The increasing evidence that slert AF i associated with a higher stroke risk®° has led to a recommendation of ‘opportunistic screen- ing for AF using pulse-taking or ECG in the most recent guidelines." This recommendation is clearly alsa valid in HTN patients because they ae ac greater risk of stroke although further research s needed 1 define best practice for younger patients with HTN and asympto- ‘matic organ damage’? ‘A numberof stucies suggest that lower BP goals reduce the fe- quency of episodes with parexysmal SVT. Lifestyle changes reduc ing the BP and AF burden may also contribute.®? “The order and type of workup of patients with arhythmias and HITN depends on varius factor including the duration and severity cof symptoms, the frequency of episodes and the potential therapeutic implication. A proposal fora standardized inital work upis shown in Figure 2. Witha CHA;DS,-VASc scare >2 (Le 22 stroke ris factors) there is sulcient risk to ether consider or recommend stroke pre= vention in patents with AF or suspected AF on the basis of (ro longed) AHRE. ‘Asa ral step, 30-day event monitoring or an implantable cariac monitor may be used to detect rare artythmis. The optimal cut-off forthe defntion of device detected AF however currently remains elsive a 6min cutoffs the mostly widely used, based onthe find- ings ofthe ASSERT tral (ASymptomatic AF and Stroke Exaluation in Pacemaker Patients and the AF Reduction Atrial Pacing)."? Closely connected to ths is the question ofthe necessary AF burden to i= tate anicoagution but a>5-6min burden s general considered 2s Spica Finally. the use of new technology that may be incorpo rated into a smartphone may be another option for recording an infrequent arrhythmic event or detecting silent AF “Consensus statements © Sient AFis commen and opportunist as screening for underyng AF should be made in HTN patients © In HTN patients with symptoms suet tie of cardia yt dsorder, the presence and typeof arrhythmia should be documented for adequate manage ment ofthe arrhyth Management approaches ‘Assen in Figure 3, the management of patients with HTN and SVT i primary driven by the type of arhythmia, HTN should be 202 soquisn0 €z ve 1sen8 Ka sagesec/sczrbre/erouerdAalyenuon'cho wopeDc}rsdnly WOH PoPeOHUNOG240 GYH Lp etal tient with HTN and Se No. ve |rscoen ; ee tenn Ceti) (rugs, ablation, anticoagulation et Diagnosis confirmed Figure 2 Proposal fo a standardized inital work up inpatients with arrhythmias and hypertension depending on the duration and severity of symptoms, the frequency of episodes and the potential therapeutic implications proactively managed, with the type of treatment determined by asso- ated compeling indications andlor comorbidities” In. general, AAS blockade with ACE inhibitors or angiotensin Il receptor block: «ers (ARB) should be considered in patients with LVH, Supraventricular tachycardia For the acute management of SVT, patient are treated tke patents with ne HTN according to published guidelines ** Vagal manoeuvres of intravenous adenosine are recommended a¢ intial therapy.” In hemodyramically unstable patents, synchronized cardioversion Is. recommended." Intravenous dltiazer, verapamil, or beta-blockers tare recommended for patients with hemodynamically stable patients*” Intravenous esmolol is especialy useful for short-term control af SVT and HT.” Catheter ablation isthe frst choice therapy forthe management ff more chronic management of SVT-%4° Similarly, focal ectopic atrial tachycardia can usually be treated by ablation. For patients who refuse catheter ablation, possible options in symptomatic patients without ventricular pre-excitation during sinus rhythm include oral betablockers, ditiazem, or verapamil. Flecainide, propafenone, or sotalol are reasonable choices in patients without structural heart disease (eg. severe LVH) who have symptomatic SVT and are not candidates for, or prefer not to undergo, catheter ablation. Atrial fibrillation ‘The priorty in the treatment of patients with AF is stroke pre- vention’"*" The default isto offer oral anticoagulation (OAC) to all AF patents except for those a low risk (defined as a CHA:DS;-VASe 1202 soquis00q ¢z vo 1son8 faq s9atsee/sez/heyetoueHdnolyanuoo cho onuopene} sci WOH PepEOHNGHypertension and cardia arthythmias 244 Stan Broa ‘AVN, AVRT, “ypicaftter” Not successtu eres Patient refuse EP study ey Enea Atria fibitation ‘Atypical trial futer ea (CrrvOr sa Rate contol Intate — Bees rythm contol No. io Loo ——> eee Figure 3 Proposed algorithm for management ofpatient wth hypertension and supraventricular tachycars. Score in males, in females}? Thus, the inital steps to identify Yow Fis’ patients in whom no antithrombotic therapy is recommended, following which OAC can be considered for those with >1 additional stroke risk factors Even singe stroke risk factor confers excess Fisk of stroke and mortality, and the net cinical benefit of treating these patientsisposiive® Uncontrolled HTN (eg, SBP >160mmHg) and other mocifable Fisk factors (eg, concomitant aspirin or non-steroidal antnfamma- tory drug treatment, excessive alcohol use) should be addressed to ‘minimize the risk ofbleeding* 'Non-vitamin K antagonist oral anticoagulants (NOACS) are the pre- ferred treatment modalty over vain K antagonists for aiconguaton based on the resus of four independent large-scale clncal tras Subgroup analyses in patients with HTN have mostly been consistent with the main outcome ofthe tril. The use of aspirin {or stroke prevention in AF is associated with minima eficacy but has a substantal bleeding risky thus, asprin & therefore no. longer recommended” Persistent as well as permanent AFis common in elderly hyperten= sive patients, often associated with MIPEF, where rhythm control ‘may not be an option, A beta-blocker or non-dihydropytidine cal= cium blocker may be considered for rate control in these patents, although RAAS blockade may aid LVH regression Digoxin may be a second-line option. 1202 soquis00q ¢z vo 1son8 faq s9atsee/sez/heyetoueHdnolyanuoo cho onuopene} sci WOH PepEOHNG242 GYH Lp etal Avil fibrilaton ablation has emerged as an effective method for the treaument of AF. In paroxysmal AF with normal sized atria, long term freedom from symptoms can be achieved in up to 80% of patients, it may require multiple procedures” In patients with per- Sstont AFand diseased aia, long-term success rates are substantially below 70%"” Ventricular arrhythmias Ventricular ectopics Ventricular archythmias are common in HTN patients and this assoc- ation may have important clinical impliations *™~"" High BP is not arrhythmogenic per se but may induce ventricular overload Ventricular arrhythmias are commonly observed in aortic stenosis, even when peripheral BP is low the frequency ofthese arrhythmias has been shown to be reduced after transcatheter aortic vale implareation* Ventricular tachycardia, ventricular fibrillation, and sudden death Hypertension isa risk factor for SCD, particulary in the context of increased LV mass” Left ventricular hypertrophy i associated with a long-term risk of SCD independent of BP, and the risk of SCD. increases progressively wth LV mass” ‘There is evidence that optimal BP control and regression of LVH, by anthypertensive treatment can help prevent cardiac arthythmins.”® Although an effect on the burden of ventricular lectopy has not been consistently observed even in the context of LWH reversal a reduced incidence of SCD has been demonstrated with effective B control and LVH regression However, the potential influence of antihypertensive drugs on the ‘ik of SCD shouldbe considered. Thazde diuretics have ben asso- ciated with an increased risk of cardiac arrhythmias, with a dose- dependent increase in SCD." Although the exaet mechanism i unkown, hypokalaemia maybe involved, with increased rk for OT prolongation. QT cspersion, and a propensty for arrhythmogenic carly and delayed ater depolarizations.” Attough BP lowering self ‘may be important in affecting the SCD risk in patients with HTN and dabetes bloctade of the RAAS seems superior to other strat- ees to preven SCD Proposal for a standardized ‘workup’ Frequent NSVT or single VPBS in patients with HTN are treated sina to those found in patents without HTN. A T2ead ECG and a 24-h Holter recording may help potentially localize site(s) of cig and quantly VPBs. Transthoracic echocardiography may be tefl to assess oer signs of ippertnave or stuchra heart, diexce and le verricur syste fnction The laters particulary important wo Kent, especialy when a high VPB burden defined as >20% of all bats in a 24-h recording, is documented®” If underlying coronary disease i suspected, with frequent VPs, assocted snp toma, or LV gytoie diction, exerce testing may be use to asses the efect on VPs and erate the presence of myocar ischemia (Figure 4). Since the presence and numberof VPBe ay be mkt by ary factors a ood biochemistry profi icing decoy (pots, magnesium, calcium), renal function, thyroid function and glucose should (Oral amietarone shouldbe used for ongoing management in patients with symptomatic SVT who are not candidates or, or prefer not to undergo, catheter ablation and in whom beta lockers, taza, Ne ange, propafenene, sotalol or verapamil are infective or contrainéeated. © “The prionty inthe tretmentof patent with AFe stroke prevention and AF patent wth HTN have a (CHALDS:-VASC score oft lest thus, fective stroke prevention may be considered with OACin sedlon to good 8P control, With addtional stroke risk factors and CHA;DS;-VASe score 22, OAC shouldbe used, a wells con trolled VKA (TTR 270%) or nonstamin K antagonist orl anticoagulants (NOAC), with a preference for the latter © Bleeding rk shouldbe astesed witha focus on modifiable bleeding rik factors mot of whch may be identified using the HAS-BLED score = The HAS-BLED score shouldbe used to identify high isk patients (score 23) for mre cre review and fallow, and to addrestreverable blending rl factors (eg uncontrolled HTN}. A hgh HAS-BLED score sine snot reason to withhold OAC, [AF ablation shouldbe used in hypertensive patients with symptomatic recurrences of AF on atiarhyth re dug therapy who prefer further rythm contel therapy and isthe fst therapy in selected invids- als as an alternative to antartythmic drug therapy depending on patient choice, benef and risk = Inpatirts wth re-enan SVT ad isthmus dependent futr. catheter ablation shouldbe used 3 thas high vecessand ow compliation ate Inpatient with severe structural heat diseases, such a severe LVH,s history of myocardial infrton tnd HF, or hemodnamcally:-sifian vabulardeeae, donot ue flesnide or propsfenone, Do not ‘se sotalol in LVH patients, or litem and verapamil HFEF patents ¥ ~ vy v . v y y 202 soquisn0 €z ve 1sen8 Ka sagesec/sczrbre/erouerdAalyenuon'cho wopeDc}rsdnly WOH PoPeOHUNOGHypertension and cardia arthythmias 243 Hypertension and ventricular arrhythmias rio Penne eave ered Raa Soe rs eet ee eptoe a eee ery ay etc ce ran erin roe erie Figure 4 Proposal for a standardized workup . Onyin rare cases does myocardial biopsy change management and the benefits of thsi ow. ‘Consider ICD implantation LVEF <35% despite goal-crected medial therapy ad sustained HTN control bbe made Moreover, ffs necessary to review prescriptions and over: the-counter agents that may lengthen the QT interval or induce sympa thetic. stimuaton, particulary if LVH is evident on ECG or echocardiography Excessive intake of alcohol or caffeine or other ‘on-pharmacelogi stimulants and recreational dug use shouldbe inves: tigated and corrected appropriately. Kentfcation of chronic exposure ‘0 high-stress conditions is important in order to counsel avoidance or ‘ways to mitigate the stress, in view ofthe facltatingefect of adrenergic stimulation on arthythmogenesis. Management approaches Management approaches or ventricular arhythmisin HTN parts tray vary widely based on the primary presentation, The mort com mon ventricular rhythms azocated with HTN are VPB, though [NSVTs have alo been observed and an affect the prognois part: larly in the context of LVH2” Although a direct relationship between VPS reduction and ant hypertensive treatment has not been clearly shown, a reduced fatal ventricular archythmia event risk has been demonstrated, and efforts to control BP remain important. Beta blockers seem to be inferior to other major antihypertensive drug clases in reducing LV mass and the major CV event risk" However, other studies have indicated overall benefit in SCD reduction with BP lowering, regardless of drug class, and have demonstrated addtional benefit with the use of beta-blockers in patients with concomitant CAD.” There is also agent-specific evidence of SCD reduction using ACEI or ARB, which appears to be independent of BPreduc- tion"? Thus, ACEI and ARB are also recommended in HTN patients at high risk for SCD. Patients with HT-induced LVH may have greater QTc dispersion, particularly in the context of hypokalaemia A relationship between (QT and RR intervals has been observed in hypertensive patients with LLVH, whichis similar to other conditions with proarshythmic poten tial including subsees of long QT syndrome."" Thus, avoiding marked hypokalaemia or anything that prolongs repolarization time may be Imnportant. wopeoeyrsdiy wou popeojunog +202 soquie20q ¢z vo 1sen8 fq soapsee/sezibree(onserlyorwon‘éno244 GYH Lp etal In asymptomatic HTN patients with normal LY systolic function and non sustained ventricular arrhythmias, there is no role forthe prophylactic ue of anarrhythmic drugs Anarrythmic drugs eg ass IC agents such as candle, are not recommended, especally where structural heart disease, such as severe LVH or LV systole dysfunction, is evident. In addon to beta blockers and ACE or ARB, catheter ablation shoul be consideredin these patens, as well as an inplantable cardioverter defxiltor (CD). Similarly, in patients with a low ejection fraction and persis- tently high frequency of ventricular ectopic bats (>15-20% of total beats in a day, or >10000 PVCS/24h) andlor associated symptoms, antiarrhythmic drugs (eg, beta blockers, aniodarone) of catheter ablation shoud be considered to potentially reverse tacycarda- induced cardiomyopathy" Final, achieving adequate BP control and promoting LVH reges- sions 2 central management goal and any combination of anthyper- tensive drg clasts shouldbe considered as needed to achieve this goal wth the conlderaons as sassed above. Inthe context of persstendyzevere LV systole dystincton (EF <35%) despite adequate medical management, including BP control, ICD implanta- tion should be considered, athough nthe absence of CAD the prog- nostic benefit is not evident.**** Complications related to arrhythmias and hypertension Heart failure Hypertension is one of the most common causes of HF and anti hypertensive therapy markedly reduces the incidence. About half ofall HF patients present a reduced ejection fraction. In general, AF Is predicted by the same risk markers predicting HF, including target organ damage.” In the context of HTN, the association with HFDEF is particularly important because the LV filing pattern |s always abnormal, requiring a greater atrial contribution”® ‘Although uncontrolled HTN is certainly a trigger for AF, consol dated organ damage is the hallmark of risk”” Thus, attention should be paid to the global management of risk (ineluding meta bolic factors and obesity) in addltion to the aggressive anthyper tensive therapy thats always required. ‘A rate control strategy is mandatory in persistent/permanent AF to facilitate LV filling, and is obtained more frequently using cardiospeciic beta-blockers."” An uncontrolled HR may lead to tachycardia:induced cardiomyopathy, with LV dilatation and Impairment. In patients with systolic HF, the combination of digoxin and a beta-blocker could be effective. In patients with HFPEF, non-dinydropyridine CCBs could be an alternative to beta-blockers. In patients with chronic HF, arhythm-control strat egy has not been demonstrated to be superior to a rate-control strategy in reducing mortality or morbidity. In acute HF, emer= gency cardioversion may be required due to hemodynamic Instability Postural hypotension Postural (orthostatic) hypotension is usually defined as drop of 20:mmtigin SBP or 1Ornbg in DBP within 2-5 min of standing uP. ‘and with light-headedness lasting a few seconds to several minutes.”” Orthostatic hypotension (OH) is common in elderly HTN patents with reported prevalence ranging fom 6% 0 30%. Due to ite asocaon wth an increased risk of fling, OH in elery pans wit HTN and AF may appropriately prevent the ure of OAC for stroke prevetion Hypertension tel and corimonly used any perteneve drugs increase the incidence of OH, The risk for OH Increases wth ageing and daberes ve to slower baroreceptor “Conrensus statements © Frequent VPBs, couplets oF nonsustained ventricular arrhythmias require a cael cial history and examination, blood chemistry a Tlead ECG, anda 244 Holter recording * Transthoracic echocardiography should be used to assess HTN patents with aehythmlas or sign of hpertensve or structural heart Ssase © Finns of frequent VPBs andlor NSVT should lead of investi for structural hear ease, lncluding transthoracleechocardography or cardiac MRL © Exerc testing oF othe funcional testing for nchaemia may be used for paints with suspected coronary disease and frequent PBs or associated symptoms both to assess suppresion or Wor- ‘ening of VPRe and to evaluate the presence of myocardial achaemia Further noninvasive testing ‘or coronary angiography may be used i required © Serological stucies, including electrolyte levels, glucose, and thyroid studies may be used to assess reversbe, secondary causes of nreased ventricular ectopy. * lenuieation of non-prescription o non-pharmaccloge sources of increased adrenergic stimula- ‘on, including ita of alcoho. caleine, and other snus including recreational drugs, should bbe documented inthe history in order to provide appropriate counseling andor hela as needed References CE CREE 202 soquisn0 €z ve 1sen8 Ka sagesec/sczrbre/erouerdAalyenuon'cho wopeDc}rsdnly WOH PoPeOHUNOGHypertension and cardia arthythmias 245 “Consensus statements © Achieving and maintaining adequate BP control should bea prenity when managing patents with HT and ventricular archythia, especially those wit severe LV systolic dysfunction (EF < 35%) * Beta-blockes shouldbe used forthe management of HTN in he setingof CAD and HF © ACE nhibtrs and ARB shouldbe used fr HTN management inpatients at igh isk for CD * Avoiding hypolalemia or QT: prolonging drugs should be a priority inthe context of HTN and LYH, © tn patents with sustained ventricular arthyhmas or frequent ne susaned ventricular artis with LW ystlc dysfunction ~ Treaurn with bet blocker, MRA and seubialsran reduces the risk ofsudden death and shouldbe used inpatients with HFFEF and ventricular arythas Catheter ablation, andlor ICD inplantaion shouldbe usedn ation to artiypertenive therapy © AnICD should be used to reduce the rk of sudden death and all cause mortality inpatients who have recovered froma ventricular arrhythmia causing haemodyrami instabilty and who are expected to sur vive fort year with good functional tus ~ In persistent, severe L systole dysincion, despite aden. BP contol and other HF management, with Frequent PBs in patents thought vo havea PVC induced earlomyopathy. ICD implantation maybe sed ifsigcanischaemic hear diseases evdent An ICD shouldbe used to reduce the risk of sudan death an aleause mortality in patents with smplomatc HF (NYHA Clas I, and an LVEF <35% despite > 3months of OMT, provided they are expected to survive substantial longer than one year with ood functional status and they have: () IHD (unless they have had an Ml inthe prior 40 days and (0 ated cardomropathy Antiarrhythmic drugs should not be used routinely inpatients with HF and asymptomatic ventricular archythmias due to safety concerns (worsering HF proarrhythmia, and death) € €€€€CE References function, impaired cardiac performance, ad stiffer arteries" Some antihypertensive and cardiodepressant medications (eg. duretcs, alpha and beta blockers, CCBs, RAAS blockers and nitrates) drugs for Parkinson's disease, and certain antidepressants and antpsy chotcs may increase the risk of OH."" Thromboembolism and bleeding risk, including safe use of antithrombotic therapy in hypertension Increased BP (SBP >130 mmHg or a diagnosis/history of HTN) dou- bles the risk of stroke in patients with AF" Oral anticoagulationt cal anicoagtart wth VKAS or NOACS reduces the stroke risk and ‘mortality in AF" but their benefit must be balanced against the risk of OAC elated major beeing (especialy ICH, du to ts ight ity rate)"®* because uncontrolled HTN (but not a diagnosis/history of HTN) increases the bleeding risk." (Optial BP contra is crac fr both stroke and bleeding rk reaucion in AF patients taking OAC. Avalable evidence from randomized tals Geaty shows a substan increase i stroke rk (loclucing both ischemic and haemorrhagic stroke) at SBP values 140 mmHg in AF patients taking warfare Ina posthoc analysis of the ARISTOTLE (Apisaban for Reduction In STroke and Other ‘Thromboembolic Events in Atal Fibrilation) trial. elevated BP (SBP 2140mmHg and/or DBP =90mmHg) at any point during the tal was associated wth an inereased risk of stroke or systemic embolism (HR 153: 95% Cl 126-186), haemorrhagic stroke (HR 1.85; 95% Cl 126-272) and a composite of major and clay relevant non- major bleeding (HR 1.14; 95% Cl 1.01-1.2) in both treatment arms (Ge. apixaban or warfarin), while a history of HTN was significantly sssovated with increased stroke but not major bleeding, Patients with uncontrolled HTN, defined asa SBP 2170-180 mm andlor DBP >100 mmHg, were excluded from all four NOAC tril, hile HTN, defined a the use of anthypertensive medications!” (or persistent SBP >140mmHg or DBP>90mmHg)" was present in 788-937" of participants. Most AF guidlines now fvour the Use of NOACS over VKAS Five 5)" Given its high prevalence in AF patents, HTN may often be the single riskfactorrequiringa decision on OAC use, and data from con- 202 soquisn0 €z ve 1sen8 Ka sagesec/sczrbre/erouerdAalyenuon'cho wopeDc}rsdnly WOH PoPeOHUNOG246 GYH Lp etal Assess the risk of bleeding (HAS-BLED) v ‘Address modifiable bleeding risk factors (e.g, uncontrolled hypertension, concomitant ASA or NSAIDs) Use informed shared decision-making with active — ‘Schedule patients with a —- HAS-BLED of 23 for a more Patient role frequent clinical follow-up Lee ycomponent | points | Calculate SAMe-TT2R2 S Sex (female) 1 ‘Age (<60 years) il + Me Medical history” 1 -— OF T Treatment 1 {interacng drugs, 2 2 e.g, amiodarone) TTobaoeo use 2 ¥ v (ohn 2 years) KA Noac R___Riaco (non-Caueasian) 2 *More than two of the folowing: hypertension, diabetes mellitus, coronary artery disease/myocardial infarction, Peripheral arterial disease, congestive heart falure, previous stroke, pulmonary disease, and hepatic or renal disease, Figure 5 Proposed algorithm for antithrombotic management of patients with hypertension and non-valvlr atrial Nbrilation, ASA. acetal acid: NSAID, non steroidal anthinfammatory drug; OAC. oral anticoagulant; VKA, vitamin K antagonist NOAC, non-tamin K oral anticoagulant. ‘SAMe-TTaR, sex female, age 60 years, medial hatory (more than two comorbidities) treatment (interacting rugs. eg amiodarone for rhythm con- ‘rel, tobacco use (doubled), race (doubled): TTR, time in therapeutic range. temporary real-world AF registries show that physicians often under= estimate the signicance of HTN as a stroke risk factor" despite clearly postive net clinical benefit (the balance of stroke reduction against serious bleeding) of OAC in patients with 21 stroke rik fac torn large contemporary AF cohorts" ‘A recent analysis showed that the threshold for OAC use at 21.7Xiyear annual stroke risk for VKAS should be decreased 10 20 9%iyear annual stroke risk with the safer NOACS.""? Two. recent analyses oflarge AF cohorts of untreated patients with one stroke risk factor reported annual stroke rates well above the NOACS threshold (1.55%? and 255-275%""), and HT was associated witha significant increase in strake risk [HR 1.71; 95% C1 148-198 (females), and 1.95; 95% Cl 1.73-2.19 (males)]"* ‘The presence of one stroke rsk factor in untreated AF patients was associated with increased rates of stroke, bleeding and death,"” and warfarin use was associated witha positive net clini cal benefit compared with no therapy or aspirin. In clinical prac tice, shared informed decision-making is useful, as AF patients commonly attribute stronger value to the avoidance of stroke than the risk of bleeding ® Health economic considerations “Taking into account the isk of CV events linked to high BP the costs ‘of untreated or inadequately controled HTN are of great relevance for any heath care system." According to metaregresion analyses, for every 10mmbg reduction in SBP the risk of major CV disease ceventsis reduced by 20%, the risk of CAD by 17% the risk of stroke bby 27%, the risk of HF by 28% and the risk of al-cause mortality by 13%""" The high prevalence ofboth HTN and AF and the increasing costs oftheir treatment are an important financial burden and there- fore many economic analyses have simed to assess the cost- efleciveness of treating these diseases”? For stroke associated with AF, the direct costs per patient are approximately 33% greater than the costs for stoke unrelated to 202 soquisn0 €z ve 1sen8 Ka sagesec/sczrbre/erouerdAalyenuon'cho wopeDc}rsdnly WOH PoPeOHUNOGHypertension and cardia arthythmias 247 ‘Consensus statements References v- © OAC shouldbe used to reduce the stroke rskin most AF ptints with HIN incling those with AF in wna HT fhe sgl aconal stroke rskfaeor Share informed decision-making on the rks and benefits of OAC therapy shouldbe used, especially where HT isthe single addtional stroke rise factor * Wellcontrolied ascoaguation nten- ne sity (1.2 TTR of265-70%) should bbe used to achieve the optimal rik benef ratio with KA therapy © Compared with VKAS, NOACS offer acon safety benefits when there 's good adherence to treatment © Optimal BP control should be used to rininize the risks of AF-eated stroke and OAC relates blessing Until more daa ae avaiable target BP value nA patients akg OAC. shouldbe < 140 mmHg SBP and 160mmég andlor DBP 100 mb but streneous efforts to contro BP shouldbe made ‘AF and are in the range of €30000 over a 2-year period for a severe ischemic stroke." In this scenario, the use of NOACS in patients with non-valwlar AF has been found to be cost cefiective"?-™ Ina series of cost effectiveness and cost-beneft aral- ses the higher intl cost of NOACs compared with warfarin was ‘offsetby the reduction in intracranial bleeding and stroke prevention, ‘making these agents cost-effective inthe long-term." Areas for further research Many areas linking HTN and cardiac arrhythmias merit additional clarfeation and further study. While perhaps rather selective, some areas ofuncertaint are summarized 38 fallow: © Hows diferent circadian BP profes, particularly blunted nocturnal BP, influence the presence of ciferent arrhythmias. © Detection and management of HTN patients with sient AF to prevent stroke risk, and whether the use of OAC in patients with HTN and slene AF resuits in a mearingll stroke reduction © Antihypertensive drugs and regression of myocardal fibrosis in patients with HTN and LVH, © Primary prevention of arrhythmia in patents with uncomplicated HIN Is there a prefered anthypertensve drug or combination? ‘© Optival antinypertensive treatment in patients with HF and pre- served ejection fraction, * Optimal BP targets in patients with HTN and OAC therapy. ‘© AF management in asymptomatic cases detected by remote mon ‘toring by implantable cardiac devices. Acknowledgements Chair, GYHL (UK, representing EHR): Co-Chair, AC. (Spain, representing the ESC Council on Hypertension); EHRA Representatives, FIM. (Spain): ASM. (Greece); JS. (Switzerland): TSP. (Serbia AO. (Turkey); Counc on Hypertension represerta- tex BW. (UK) GAS. (tay); TK. (Sweden): MHLO. (Oenmark HRS representative: WST. (USA): APHRS representative: CEC. (Tavan); SOLEACE representative, MF. (ral); Heath Economie perspective, GB, ([taly). Conflict of interest: See description inthe fll paper published in EUROPACE (dot: 10.1093/eurepace/eux09"), References "Ya KH, Tee HF Hypertension and card atyehmi: a revi ofthe ep camiloge prphynlloy an cnc! inpbeatons. Ham Hypenene| 008220" 2 Ee Kote § Seman Shimad K,Karo K Vito an ab tory blood pressure varablity 8 predktors of indent edonsculr versa patos with hypertension Am) Hyper 207225962 968. 3. Gowte A Kalra JM Agia LAr J Cabrera JA, Chan 8A, Ch $8, (Cora D, Das A, Dates D, Fal G, Gas M, Hatem SN. Hee Finds, Ho SY, Hot le Kin YH, Lp G Ha CS, Mares GM, Moray K Nopuri A. Sanders P. 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