Cardiovascular Medicine

Kardiovaskuläre Medizin – Médecine cardiovasculaire 9 21. 9. 2016 Cardiovascular Medicine 225 René Lerch Myocardial energy metabolism in heart disea...
15 downloads 0 Views 4MB Size
Kardiovaskuläre Medizin – Médecine cardiovasculaire

9 21. 9. 2016

Cardiovascular Medicine 225 René Lerch Myocardial energy metabolism in heart disease: Is it clinically relevant?

231 Tardu Özkartal, Laurent Haegeli, Thomas Wolber, et al. Akuter Ablationserfolg supraventrikulärer Tachykardien

237 Simon von Gunten, Jean-Luc Crevoisier, Michael Kühne, et al. To explant, or not to explant, that is the question Official journal of the Swiss Society of Cardiology, the Swiss Society of Hypertension, the Swiss Society of Angiology and the Swiss Society of Paediatric Cardiology www.cardiovascmed.ch

245 Mirdita Gaxherri, Jürg Schläpfer A strange ECG

TABLE OF CONTENTS

223

Editorial Board

Section editors

Prof. Dr. Thomas F. Lüscher, Zürich (ed. in chief); Prof. Dr. François

The interesting ECG: Dr. Michael Kühne, Basel; Dr. Jürg Schläpfer,

Mach, Genève (ed. in chief); PD Dr. Jan Steffel, Zürich (deputy editor);

Lausanne. Images in cardiovascular medicine: Dr. Alain Delabays,

Dr. Philippe Meyer, Genève (deputy editor); Dr. Natalie Marty

Morges; Prof. Dr. Michel Zuber, Othmarsingen. The new device:

(Managing editor); Dr. Katharina Blatter (Managing editor)

PD Dr. Haran Burri, Genève; Prof. Dr. Stephan Windecker, Bern. The new compound: PD Dr. Georg Ehret, Genève. Evidence-based

Editors

cardiology: Prof. Dr. Heiner Bucher, Basel; PD Dr. Jens Hellermann,

Prof. Dr. Paul Erne, Luzern; Prof. Dr. Augusto Franco Gallino, Bellinzona;

Altstätten; PD Dr. Jörg Muntwyler, Kloten

Prof. Dr. René Lerch, Puplinge / Genève (Senior editor); Prof. Dr. Bernhard Meier, Bern; Prof. Dr. Matthias Pfisterer, Basel;

Advisory Board

Prof. Dr. Hans Rickli, St. Gallen; Prof. Dr. Christian Seiler, Bern;

The members of the Advisory Board are listed on www.cardiovascmed.ch

Prof. Dr. Bernard Waeber, Lausanne

Review article René Lerch

225

Transport

Glycolysis

ATP

Lactate PDH

Fatty acid Ketone bodies Amino acids

Myocardial energy metabolism in heart disease: Is it clinically relevant?

Structure

ATP

Glycogen

Glucose

Contraction

Oxidative phosphorylation

CrP

Acetyl-CoA

Andreas Grüntzig Lecture of the Swiss Society of Cardiology Congress 2016 in Lausanne.

Respiratory chain

O2

ß-oxidation Triglycerides

H2O

Krebs cycle

NADH

Mitochondria

O2

Original article Tardu Özkartal, Laurent Haegeli, Thomas Wolber, Nazmi Krasniqi, Ardan M. Saguner, Alexander Breitenstein, Corinna Brunckhorst, Thomas F. Lüscher, Firat Duru, Jan Steffel

Akuter Ablationserfolg supraventrikulärer Tachykardien

231

Eine aktuelle Zusammenstellung supraventrikulärer Tachykardien sowie der akuten Erfolgs- und Komplikationsraten von Ablationsbehandlungen eines universitären Zentrums mit interessanten Ergebnissen.

Case reports Simon von Gunten, Jean-Luc Crevoisier, Michael Kühne, Tobias Reichlin, Stefan Osswald, Christian Sticherling, Beat Schaer

To explant, or not to explant, that is the question

237

Recurrent surgery in device patients carries a certain risk of infection and should therefore be kept to a minimum. But what should be done with a redundant pacemaker?

Swissness in a Nutshell Gianni Haver and Mix & Remix 130 pages. Paperback. CHF 22.90 ISBN 978-3-905252-65-1

This illustrated volume aims to answer a simple question: What is Switzerland? This is the third volume in Bergli Books’ In a Nutshell series, which also includes Swiss History in a Nutshell and Swiss Democracy in a Nutshell, and which is the best source for entertaining and illuminating guides to Swiss culture. Printed and bound in Switzerland

Bergli Books | Steinentorstrasse 11 | CH-4010 Basel | Tel. +41 (0)61 467 85 65 | Fax +41 (0)61 467 85 76 | [email protected]

Books …feel at home in Switzerland

www.bergli.ch

For anyone who wants to understand what the Swiss are all about:

TABLE OF CONTENTS

224

Elefteri Buset, Richard Kobza, Florim Cuculi

A benign cause for voltage loss in the precordial leads

239

A simple method to identify one cause of voltage loss on the ECG.

Diego Arroyo, Serban Puricel, Mario Togni, Stéphane Cook

HeartMate PHP axial pump for high-risk PCI_______________________________

241

The interesting ECG Mirdita Gaxherri, Jürg Schläpfer

A strange ECG

245

An avoidable cause of life-threatening arrhythmia.

Liederbuch in zeitgemässer Ausgabe Ben Vatter  MANI MATTER LIEDERBUCH

mit Illustrationen von Silvan Zurbriggen

2015. Geb., 152 Seiten CHF 38.– / EUR 38,– ISBN 978-3-7296-0905-1

Das von Ben Vatter erstellte neue Noten- und Textbuch ist eine zeitgemässe Ausgabe sämtlicher Lieder Mani Matters, von denen Originalaufnahmen existieren, sowie der bekanntesten von Fritz Widmer und Jacob Stickelberger postum eingespielten Aufnahmen. Die Schreibweise der Texte wurde grundsätzlich von Mani Matter übernommen; lediglich offensichtliche Inkonsequenzen wurden korrigiert und teilweise Wörter oder Sätze den Originalaufnahmen entsprechend angepasst. Zu vielen Chansons sind Hintergrundinformationen oder passende Zitate zusammengetragen. Zahlreiche Illustrationen des Zeichners Silvan Zurbriggen flankieren die Lieder und nähern sich ihnen auf eine neue, visuell originelle Weise an. Zytglogge Verlag | Steinentorstrasse 11 | CH-4010 Basel Tel. +41 (0)61 278 95 77 | Fax +41 55 418 89 19 | [email protected]

Impressum Cardiovascular Medicine Official publication of the Swiss Society of Cardiology, the Swiss Society for Angiology, the Swiss Society of Hypertension and the Swiss Paediatric Cardiology Society. Contact: Gisela Wagner, CVM Editorial office, EMH Medical Publishers Ltd., Farnsburgerstrasse 8, 4132 Muttenz, Phone +41 (0)61 467 85 52, Fax +41 (0)61 467 85 56, [email protected], www.cardiovascmed.ch Online manuscript submission: http://www.edmgr.com/cvm Publishing company: EMH Medical Publishers Ltd., Farnsburgerstrasse 8, 4132 Muttenz, Phone +41 (0)61 467 85 55, Fax +41 (0)61 467 85 56, www.emh.ch

Marketing / Advertising: Dr. phil. II Karin Würz, Head of Marketing and Communication, Phone +41 (0)61 467 85 49, Fax +41 (0)61 467 85 56, [email protected] Subscription: EMH Medical Publishers Ltd., Subscriptions, Farnsburgerstrasse 8, 4132 Muttenz, Tel. +41 (0)61 467 85 75, Fax +41 (0)61 467 85 76, [email protected] Retail price (excl. postage): CHF 125.–, students CHF 63.–. Postage prices and single issues see www.sanp.ch ISSN: print version: 1664–2031 / online version: 1662-629X Mode of publication: 11 issues per year.

© EMH Swiss Medical Publishers Ltd. (EMH), 2016. «Cardiovascular Medicine» is an open access publication of EMH. EMH Swiss Medical Publishers Ltd. grants to all users on the basis of the Creative Commons license «Attribution-NonCommercial-NoDerivatives 4.0 International» for an unlimited period the right to copy, distribute, display, and perform the work as well as to make it publicly available on condition that: (1) the work is clearly attributed to the author or licensor; (2) the work is not used for commercial purposes and (3) the work is not altered, transformed, or built upon. Any use of the work for commercial purposes needs the explicit prior authorisation of EMH on the basis of a written agreement.

Hinweis: Alle in dieser Zeitschrift publizierten Angaben wurden mit der grössten Sorgfalt überprüft. Die mit Verfassernamen gezeichneten Veröffentlichungen geben in erster Linie die Auffassung der Autoren und nicht zwangsläufig die Meinung der Redaktion von «Cardiovascular Medicine» wieder. Die angegebenen Dosierungen, Indikationen und Applikationsformen, vor allem von Neuzulassungen, sollten in jedem Fall mit den Fachinformationen der verwendeten Medikamente verglichen werden. Production: Schwabe AG, Muttenz, www.schwabe.ch

REVIEW ARTICLE

225

Andreas Grüntzig Lecture of the Swiss Society of Cardiology Congress 2016 in Lausanne

Myocardial energy metabolism in heart disease: Is it clinically relevant? René Lerch Cardiology Division, University of Geneva, Switzerland

is derived in the mitochondria from oxidative degra-

Summary

dation of metabolic substrates taken up by the cardiac

Students of cardiac disease acquire, with good reason, knowledge on clinical presentation and associated mechanical and electrical derangements of heart function. Myocardial energy metabolism has largely remained a research topic without much impact on clinical cardiology. However, continuous energy production in the heart muscle is crucial for proper cardiac function. This is achieved by pronounced flexibility in fuel selection for energy production allowing constant adaptation to changes in both energy needs and metabolic environment. It is increasingly recognised that heart disease is often associated with loss of metabolic flexibility, which may contribute to cardiac dysfunction. In this review article metabolic changes in two clinically important conditions, during postischaemic reperfusion and in heart failure, are presented and the clinical relevance discussed. Barriers for translational research are emphasised, and current and emerging imaging modalities allowing metabolic measurements, not only in the experimental setting but also in hearts of patients, are critically discussed. Key words: myocardial metabolism; reperfusion injury; heart failure; metabolic imaging; translational cardiology.

myocytes [1, 2]. The remainder originates mainly from substrate-level phosphorylation during glycolysis of glucose in the cytoplasmic compartment (fig. 1). The term “substrate” denotes the “fuel” used by the cell for energy production. The healthy heart can utilise almost every metabolic substrate supplied by coronary circulation and can rapidly switch between substrates without affecting contractile performance [3]. Circulating substrates include glucose, lactate, pyruvate, fatty acid, ketone bodies and amino acids. The capacity of the myocardium to adapt energy metabolism to substrate availability with unaltered contractile function is often referred to as “metabolic flexibility”. Metabolic flexibility is a hallmark of healthy myocardium and is lost in cardiac disease conditions including ischaemic heart disease, heart failure, diabetes and obesity. Loss of metabolic flexibility may contribute to cardiac dysfunction [3–7]. In this review article I will focus on metabolic changes in two common disease conditions: (1) ischaemic heart disease, specifically myocardium that is reperfused after an ischaemic insult, and (2) heart failure. Known metabolic diseases such as diabetes

Introduction Metabolic changes in the heart muscle are barely ad-

and obesity are not addressed and the interested reader is referred to excellent review articles on these topics [2, 8–10].

dressed during medical education. However, most cardiac diseases are associated with alterations in energy metabolism, which may contribute to cardiac dysfunction and provide targets for therapeutic interventions. My personal interest in energy metabolism was kindled more or less by chance during my first training position in cardiology at the Cardiology Division of the University Hospital in Zurich, when I was assigned by the head of cardiology, Professor Wilhelm Rutishauser, to an experimental study on myocardial high-energy phosphate content during coronary flow reduction. The present article summarises some lessons I learnt during my continuing research interest in myocardial energy metabolism since the early 1970s. Cardiac function requires uninterrupted synthesis of adenosine triphosphate (ATP), of which more than 90%

CARDIOVASCULAR MEDICINE – KARDIOVASKULÄRE MEDIZIN – MÉDECINE CARDIOVASCULAIRE

Abbreviations AHA: American Heart Association ATP: adenosine triphosphate CrP: creatine phosphate FADH2: flavin adenine dinucleotide (reduced form) 18 FDG: fluorine-18 labeled deoxyglucose MRS: magnetic resonance spectroscopy NADH: nicotinamide adenine dinucleotide (reduced form) PDH: pyruvate dehydrogenase PET: positron emission tomography PGC-1: peroxisome proliferator-activated receptor gamma coactivator 1-alpha PPAR: peroxisome proliferator-activated receptor alpha

2016;19(9):225–230

REVIEW ARTICLE

226

seems to depend largely on supply of each substrate; Transport

fatty acids account for approximately 70% of total oxygen consumption [14].

Glycolysis

ATP

Lactate PDH

Fatty acid Ketone bodies Amino acids

and (3) under resting conditions in the fasting state,

Structure

ATP

Glycogen

Glucose

Contraction

Oxidative phosphorylation

CrP

Acetyl-CoA

fluencing substrate selection of the cardiomyocytes for in experimental models that allow for control of sub-

O2 Krebs cycle

During the following decades cellular mechanisms inenergy metabolism have been intensely investigated

Respiratory chain

ß-oxidation Triglycerides

H2O

strate supply, including perfused heart preparations and isolated cardiomyocytes in culture. It has become evident that metabolic pathways interact and recipro-

NADH

Mitochondria

O2

cally inhibit each other depending on substrate availability; this is known as “substrate competition” [2]. Substrate use in some current physiological conditions is depicted in (fig. 2) [2, 15]. Under resting conditions after an overnight fast, fatty acids are the main substrate for

Figure 1: Schematic overview of myocardial energy metabolism. Cardiomyocytes can utilise a broad spectrum of metabolic substrates for energy production (left part of the figure). With the exception of glucose, catabolism of substrates occurs in the mitochondria, which produce the bulk of ATP for contraction and other cellular functions. Electrons originating from β-oxidation of fatty acid and from the Krebs cycle are first transferred to NAD + (or FAD) to form NADH (or FADH2), then fed into the respiratory

myocardial metabolism. In contrast, glucose predomi-

chain, and finally combine with oxygen (O2) to form H2O. Respiratory chain drives oxidative phosphorylation with resultant synthesis of ATP from adenosine diphosphate. Glucose and fatty acid extracted by the cardiomyocytes can either be channelled directly to oxidation in the mitochondria or first be stored in the cytoplasm as glycogen or triglycerides, respectively. Importantly, glycolysis of glucose in the cytoplasm produces a small amount of ATP by substrate-level phosphorylation. Pyruvate dehydrogenase regulates formation of acetyl-CoA from glucose and lactate, and is a key regulatory step for substrate competition. ATP = adenosine triphosphate; PDH = pyruvate dehydrogenase; NAD + = nicotinamide adenine dinucleotide; FAD = flavin adenine dinucleotide; CrP = creatine phosphate.

and pyruvate. Substrate flexibility for energy produc-

nates after a carbohydrate-rich meal, and lactate during intense exercise. Utilisation of ketone bodies is increased during prolonged fasting but they remain a minor fuel in the healthy heart, similar to amino acids tion allows the normal heart to maintain normal function during changing metabolic environments and demands.

The challenge of assessing myocardial substrate metabolism in patients Coronary sinus catheterisation, as used by Richard Bing, has two major limitations for the characterisation of myocardial metabolism in cardiac patients.

Metabolic flexibility – A hallmark of the healthy heart

First, the method allows measurement of global substrate extraction across the entire heart, but cardiac disease conditions, above all coronary artery disease,

A seminal step towards understanding substrate flexi-

exhibit marked regional differences in myocardial

bility of myocardial energy metabolism was the work

metabolism. Second, the method does not provide

of Richard Bing (1909–2010). Born in Nuremberg,

information on the intracellular fate of extracted sub-

Richard Bing emigrated from Germany in 1935, ob-

strates. In fact, extracted fatty acid and glucose may

tained a medical degree at the University of Bern be-

not be channelled to energy metabolism, but be stored

fore embarking in the USA on an outstanding career in

as triglycerides or glycogen, respectively, or enter

the rapidly evolving domain of cardiology. At John

other pathways required for cellular structure or func-

Hopkins University in Baltimore he set up the first

tion [7].

catheterisation laboratory for congenital heart disease

In the second half of the 1970s, positron emission to-

in 1945 [11, 12]. When, during right heart catheterisa-

mography (PET), a new radionuclide imaging modality,

tion, he entered in error the coronary sinus, he recog-

emerged and held great promise for the assessment of

nised the potential of this manoeuvre to enable meas-

substrate metabolism in different regions of the heart;

urement of the uptake of different metabolic substrates

in addition, it is noninvasive [16]. PET involves short-

in the human heart [13]. In pioneering studies in the

lived cyclotron-produced radionuclides such as car-

early 1950s, he demonstrated that: (1) the human heart

bon-11, nitrogen-13, and oxygen-15, with half-lives of

can metabolise simultaneously glucose, lactate, pyru-

20.3, 10.0 and 2.1 minutes, respectively. These radio-

vate, fatty acid, ketone bodies and amino acids for en-

nuclides offer at least three major advantages for the

ergy production; (2) the pattern of substrate oxidation

assessment of myocardial substrate metabolism: (1)

CARDIOVASCULAR MEDICINE – KARDIOVASKULÄRE MEDIZIN – MÉDECINE CARDIOVASCULAIRE

2016;19(9):225–230

REVIEW ARTICLE

227

they can be incorporated into biomolecules such as

after a short time interval [17, 18]. Fluorine-18 is another

metabolic substrates without altering the molecular

positron-emitting radionuclide that has attracted a lot

structure and, accordingly, the metabolic behaviour;

of interest in PET. Because of its somewhat longer half-

(2) the content of the radionuclides can be quantified in

life of 110 minutes, it allows transport of labelled com-

each region of the heart with PET; and (3) the short half-

pounds over some distance, obviating the need of an

lives of the radionuclides allow repetition of the study

in-hospital cyclotron. Although fluorine is not a natural component of metabolic substrates, it can substitute for a hydroxyl group in a number of parent mole-

Rest

Fasting

Postprandial

Exercise

Fatty acid

Fatty acid

Glucose

Lactate

Glucose Lactate

Ketone bodies Amino acids Glucose Lactate

Lactate Fatty acid

Fatty acid Glucose

(carbohydrate-rich meal)

cules. Fluorine-18-labelled deoxyglucose (18FDG) has proved useful for the delineation of regional glucose uptake in the myocardium [19]. What kind of metabolic information is obtained from PET with labelled metabolic substrates? I had the opportunity to participate during a research fellowship at Washington University St. Louis in early experimental studies designed to define the potential of PET with C-labelled palmitic acid for the assessment of regional

11

myocardial fatty acid metabolism. After intravenous injection of 11C-palmitate, metabolic information is derived (1) from accumulation 11C-radioactivity in different regions of the myocardium, and (2) from release of the 11C-label, and hence the clearance rate of radioactiv-

ATP

ity, from the myocardium. Accumulation of the label reflects myocardial fatty acid uptake [20]. Clearance of C-radioactivity provides information on the rate of in-

11

Work

tracellular fatty acid metabolism (fig. 3) [21, 22]. The

Figure 2: Substrate flexibility in healthy heart. Substrate pattern of energy metabolism in different physiological conditions. Data from reference [15].

clearance curve of radioactivity from 11C-palmitate exhibits a biexponential pattern composed of an early rapid component, corresponding to clearance of label from palmitate that is rapidly oxidised, and a late slow component, reflecting slow clearance of radioactivity

C-palmitate

11

from palmitate that is first incorporated into triglycer-

C-accumulation Myocardial 11C-activity

11

Clearance of 11C-label

poxic myocardium the early rapid clearance component of radioactivity from 11C-palmitate was slower,

2.0

consistent with reduced fatty acid oxidation [21, 22]. Although PET with labelled metabolic substrates al-

1.0

0.5

ides and other lipid esters [21, 23]. In ischaemic and hy-

lowed for the first time noninvasive assessment of re-

r =.99 k 0 0.065 10

20

30

40

50

TIME (min)

60

70

gional substrate metabolism, quantification of the rate of substrate oxidation in absolute terms remained a major challenge because of the rather complex intra-

Fatty acid uptake

Intracellular metabolism

Figure 3: Assessment of fatty acid metabolism by use of positron emission tomography with 11C-palmitate. After intravenous injection, accumulation of 11C-radioactivity in an early scan reflects palmitate uptake in the different regions of left ventricle (left). Clearance of 11C-radioactivity measured in a selected region by sequential scans provides information on the intracellular fate of the tracer (right). The rapid clearance component in the semilogarithmic graph, predominating during the first 20 minutes after tracer injection, reflects clearance of the label from 11C-palmitate that is rapidly channelled to mitochondrial β-oxidation, the late slow component clearance of carbon-11 from tracer first incorporated into triglycerides [21–23]. (Reprinted from: Lerch RA, Ambos HD, Bergmann SR, Welch MJ, Ter-Pogossian MM, Sobel BE. Localization of viable, ischemic myocardium by positron-emission tomography with 11C-palmitate. Circulation. 1981;64(4):689–99, with permission.

CARDIOVASCULAR MEDICINE – KARDIOVASKULÄRE MEDIZIN – MÉDECINE CARDIOVASCULAIRE

cellular metabolism of extracted substrates, with channelling of the tracer to several intracellular pools with different turnover rates [23]. Therefore, strategies have been developed to monitor only a selected segment of metabolism of a given substrate [18]. The bestknown example is measurement of myocardial glucose uptake with 18FDG.18FDG is a structurally modified glucose analogue molecule that is taken up by the myocardium similarly to naturally occurring glucose, but which is not further metabolised in the cardiomyocytes and allows quantification of regional myocardial glucose uptake by use of mathematical modelling [19].

2016;19(9):225–230

REVIEW ARTICLE

228

An emerging approach for the assessment of myocar-

vation, we observed by direct metabolic measure-

dial substrate metabolism is magnetic resonance spec-

ments in isolated perfused rat hearts subjected to

troscopy (MRS) of C-labelled molecules. MRS offers

40 minutes of no-flow ischaemia, a reduction in fatty

the unique opportunity not only to noninvasively de-

acid oxidation and a concomitant increase of glucose

tect the isotope in the myocardium, but also to iden-

oxidation early during reperfusion [32]. This degree of

13

tify in which molecules and in which position in the la-

ischaemic injury corresponds to evolving myocardial

belled molecules the isotope resides. Until recently, the

infarction. Rapid activation of glucose oxidation in ad-

application of carbon-13 MRS has been limited by the

vanced ischaemic injury was mediated by activation of

low abundance and low signal intensity of 13C-labelled

the regulatory enzyme of glucose oxidation, PDH, by

compounds in the heart, even after administration of

cytosolic calcium overload [33]. Concomitant reduction

C-labelled substrates. More recently, enhancement of

of fatty acid oxidation is most likely secondary, and re-

signal intensity by several magnitudes has been

flects inhibition of this pathway by substrate competi-

13

achieved by hyperpolarisation of

13

C-labelled sub-

tion during activation of glucose oxidation.

strates [24]. After intravenous injection the method al-

The crucial question from the clinical point of view is

lows not only detection of uptake and global clearance

whether partial loss of metabolic flexibility during

of the 13C-label, but also tracking of the isotope in dif-

postischaemic reperfusion, with a shift from fatty acid

ferent downstream metabolites [25, 26]. Initial preclini-

to glucose oxidation, is an adaptive, favourable re-

cal studies with hyperpolarised C-pyruvate labelled

sponse, which prevents cardiomyocyte dysfunction

in position 1 for the assessment of flux rate through the

and cell death or rather contributes to myocardial in-

pyruvate dehydrogenase (PDH) reaction [24, 27], or la-

jury. Evidence from our group [32] and others [34, 35] in-

13

belled in position 2 for the assessment of Krebs cycle

dicates that glucose as metabolic substrate is essential

activity [24, 28], have provided the proof-of-principle.

for recovery of cardiomyocytes early during reperfu-

One major challenge of this approach is the rapid sig-

sion. If, after 40 minutes of no-flow ischaemia, isolated

nal decay of hyperpolarised carbon-13 in the order of 1

perfused hearts were reperfused with either fatty acid

minute. Although the method is at an early stage, it has

plus glucose or with glucose alone, recovery of contrac-

the potential to enhance knowledge on regional myo-

tile function was virtually identical (fig. 4) [32]. How-

cardial substrate metabolism in both clinical and re-

ever, if glucose was withdrawn from the perfusate at

search settings.

the moment of reperfusion and the hearts reperfused

At present, cardiac metabolic imaging is applied

with fatty acid as a sole substrate, recovery of contrac-

mainly in research on cardiac metabolism. Widespread

tile function was much worse and more creatine ki-

clinical application of both PET and MRS is hampered

nase was released into the coronary effluent as sign of

by a number of limitations. First, the costs involved in

increased irreversible injury [32]. Accordingly, unlike

these technologies are high. Second, alternative, less

in healthy myocardium with preserved substrate flex-

expensive imaging methods provide sufficient infor-

ibility, contractile function and survival of postischae-

mation for clinical decision making in most cases,

mic myocardium is critically dependent on the pres-

including assessment of myocardial viability [29].

ence of glucose. The precise mechanism of the

Finally, although the potential for detailed characteri-

protective effect of glucose during reperfusion is not

sation of cardiomyocyte dysfunction in cardiac dis-

entirely clarified. However, Jeremy et al. observed that

ease is large, definition of the clinical impact of meta-

inhibition of glycolysis during the first 30 minutes of

bolic indices on patient management requires further

reperfusion results in aggravation of intracellular cal-

research.

cium accumulation, triggering lethal contracture of the cardiomyocytes [34, 36]. It is likely that ATP pro-

Loss of substrate flexibility in heart disease: does it matter for outcome?

duced during glycolysis by substrate-level phosphorylation during the cytoplasmic compartment is essential early in postischaemic reperfusion to support the ion

Postischaemic reperfusion

pumps necessary for restoration of normal ion homeo-

Shortly after the introduction of reperfusion therapy

stasis [37].

of myocardial infarction into clinical practice in the

A clinically important message of the protective effect

1980s, Schwaiger et al. from the University of Califor-

of glucose early during reperfusion is that myocardial

nia Los Angeles observed, when using PET with 11C-pal-

salvage achieved by timely reperfusion can be further

mitate and 18FDG in a dog model, that the reperfused

enhanced by an intervention applied during the early

region seems to oxidise less fatty acid and take up

reperfusion period. However, the protective effect of

more glucose [30, 31]. Consistent with this in vivo obser-

glucose during postischaemic reperfusion observed in

CARDIOVASCULAR MEDICINE – KARDIOVASKULÄRE MEDIZIN – MÉDECINE CARDIOVASCULAIRE

2016;19(9):225–230

REVIEW ARTICLE

229

In advanced heart failure glucose oxidation also beLV pressure development

35

changes during progression from compensated hyper-

30

trophy to heart failure in a mouse model with targeted overexpression of angiotensinogen in the myocar-

mm Hg

25

dium [49, 50]. Because there is abundant angiotensin

20

converting enzyme in the myocardium, the myocar-

15

dial tissue is chronically exposed to increased levels of angiotensin II, which is known to contribute to mala-

10

daptive remodelling and progression into heart failure

5

[51]. After 1 year, all mice exhibited left ventricular hy-

0 Metabolic substrate during reperfusion

comes reduced [48]. We have studied metabolic

Palmitate + Glucose

Glucose

Palmitate

*p 100 ms,

von sechs interventionellen Rhythmologen (FD, JS, CB,

das Auftreten von Doppelpotentialen mit konstantem

LH, TW, NK), in der Regel mit Assistenz mindestens

Intervall entlang der Ablationslinie sowie der Nach-

eines Elektrophysiologie-Fellows, durchgeführt. Nach

weis einer kranio-kaudalen Aktivierung der lateralen

Lokalanästhesie mit Lidocain und Punktion der

rechten Vorhofwand bei Stimulation aus dem proxi-

rechten Femoralvene wurden üblicherweise drei

malen Koronarsinus bzw. gegenläufiger Aktivierung

diagnostische Katheter (rechter Vorhof / Koronarsinus,

während Stimulation mit dem Ablationskatheter

His-Bündel und rechtsventrikulärer Apex) positio-

lateral der Ablationslinie als Erfolgskriterium (bidirek-

niert. In Ausnahmefällen wurde die Untersuchung in

tionaler Block). Bei atrialen Tachykardien und

Intubationsnarkose durchgeführt. Zur Ablation einer

atypischem Vorhofflattern wurde in der Regel eine Ver-

linksseitigen Rhythmusstörung erfolgte eine trans-

langsamung bzw. Verlängerung der Zykluslänge vor

septale Punktion und in einzelnen Fällen eine arteri-

Terminierung der Tachykardie während der Ablation

elle Punktion mit retrograd aortalem Zugang. Vor

sowie eine anschliessende Nichtinduzierbarkeit trotz

einer Ablationsbehandlung von isthmusabhängigem

aggressiver Stimulation als Erfolg gewertet.

Vorhofflattern wurde in der Regel auf eine transösophageale Echokardiographie (TEE) zum Ausschluss int-

Statistik

rakardialer Thromben verzichtet, wenn zum Zeitpunkt

Sämtliche statistischen Analysen wurden mit Mi-

der Ablation ein Sinusrhythmus vorlag oder eine suffi-

crosoft Excel 2010 durchgeführt. Ein p-Wert 2 Tage einer Hospitalisation mit mehr als zwei Übernachtungen.

2016;19(9):231–236

ORIGINAL ARTICLE

235

Komplikationen

AVNRT (1,6%) behandelt, wobei auch fokale atriale

Schwerwiegende Komplikationen traten bei vier Un-

Tachykardien mit 5,6% eher selten waren.

tersuchungen (1,1%) auf. Während der Ablation eines slow-pathway des AV-Knotens aufgrund einer typi-

Akuter Ablationserfolg

schen AVNRT kam es bei 2 Patienten (1,1% aller AVNRT-

In derselben Registerstudie aus Spanien [8] wurde die

Ablationen) zu einer persistierenden kompletten AV-

AVNRT in 98% der Fälle erfolgreich abladiert, das Vor-

Blockierung. Einer der Patienten blieb während sowie

hofflattern in 97% und das WPW-Syndrom in 91%. Die

nach dem Eingriff aufgrund eines hohen Ersatzrhyth-

geringste Erfolgsrate bestand mit 85% bei der fokalen

mus oligosymptomatisch, so dass bis dato insbeson-

atrialen Tachykardie. In einer Meta-Analyse aus dem

dere auf Wunsch des Patienten, von einer Schritt-

Jahre 2009 [2], bei der insgesamt 57 Studien mit über

macher-Implantation abgesehen wurde. Beim zweiten

9 000 Patienten analysiert wurden, waren die Erfolgs-

Patienten hingegen musste ein Zweikammerschritt-

raten vergleichbar. Diese betrugen für AVNRT 94%, für

macher implantiert werden (0,56% der AVNRT-Ablatio-

Vorhofflattern 92% und für AVNRT kombiniert mit

nen bzw. 0,29% aller Ablationen für SVT).

WPW 91%. Diese Zahlen decken sich weitgehend mit

Bei einem Patienten mit isthmusabhängigem Vorhof-

unseren Ergebnissen mit akuten Erfolgsraten von je

flattern kam es postinterventionell zu einem grossen

100% bei AVNRT und isthmusabhängigem Vorhof-

Hämatom in der rechten Leiste im Bereich der Punkti-

flattern, von 89% bei WPW und 85% bei fokaler atrialer

onsstelle, was die Gabe von zwei Erythrozytenkonzen-

Tachykardie, was zeigt, dass die Ablation von SVT

traten erforderlich machte. Der Patient stand unter

heute eine Routineeingriff mit beeindruckend hohem

einer Behandlung mit einem Vitamin-K-Antagonisten

akuten Erfolg ist.

und der INR betrug zum Zeitpunkt der elektrophysio-

Die längerfristigen Erfolgsraten für supraventrikuläre

logischen Untersuchung 2,6. Das Hämatom musste

Tachykardien sind gemäss mehreren Studien ebenfalls

aufgrund einer Superinfektion im Verlauf operativ

hoch. In einer früheren Zusammenstellung aus Zürich

ausgeräumt werden und heilte schliesslich folgenlos

[9] betrug diese bei 243 konsekutiven Patienten 99%

ab. Bei einem Patienten konnte postinterventionell

nach sechs Monaten. In anderen Studien wurden Rezi-

nach linksseitiger WPW-Ablation echokardiographisch

divraten von 1,5% für AVNRT [10] (bei 1 419 Patienten

ein kleiner, hämodynamisch nicht relevanter Peri-

über 63 Monate), von 4% für WPW [11] (nach median 48

karderguss festgestellt werden, welcher keine thera-

Monaten), von 10% für fokale atriale Tachykardien [12]

peutischen Konsequenzen nach sich zog.

(bei 80 Patienten über 33 Monate) sowie von 11% für ty-

Periinterventionelle Todesfälle traten nicht auf.

pisches Vorhofflattern (in einer Meta-Analyse [13] mit über 10 000 Patienten) beschrieben. Eine Analyse der

Diskussion

Rezidivraten war nicht Teil unserer aktuellen Studie, sodass diesbezüglich keine Aussagen für unsere Studi-

Bei der vorliegenden Studie handelt es sich unserem

enpopulation getroffen werden können und hierfür

Wissen nach um die erste aktuelle Zusammenstellung

weitere Untersuchungen erforderlich sind.

supraventrikulärer Tachykardien sowie der akuten

Fast die Hälfte aller Untersuchungen wurde ambulant

Erfolgs- und Komplikationsraten von Ablations-

durchgeführt; nur 7% der Patienten blieben länger als

behandlungen eines universitären Zentrums in der

eine Nacht im Spital. Diese Ergebnisse sind mit einer

Schweiz. Es zeigten sich verschiedene interessante

früheren Studie aus Frankreich und der französischen

Ergebnisse.

Schweiz [14] vergleichbar. In letzterer Studie mussten

Prävalenz supraventrikulärer Tachykardien

onen im Bereich der Einstichstelle oder aufgrund von

In einer grossen Registerstudie aus Spanien [8] mit ins-

Lungenembolien rehospitalisiert werden.

lediglich 0,6% der Patienten aufgrund von Komplikati-

gesamt 7659 Patienten war die AVNRT mit 37% die am häufigsten interventionell therapierte supraventriku-

Komplikationen bei SVT Ablation

läre Tachykardie, gefolgt von typischem Vorhofflattern

Die Komplikationsraten lagen bei den oben zitierten,

mit 32%. Am seltensten wurde mit 4,3% der Fälle die

internationalen Studien je nach Rhythmusstörung

fokale atriale Tachykardie behandelt. Auch in unserer

zwischen 0,5 und 2,9%, die Mortalität jeweils bei 0,02%

Studienpopulation war die typische AVNRT mit 48%

und damit sehr tief. Die häufigsten Komplikationen in

die am häufigsten abladierte SVT, gefolgt von isth-

der erwähnten Meta-Analyse [2] waren mit 1,4% ein

musabhängigem Vorhofflattern mit 18%. Am seltens-

kompletter AV-Block mit Implantation eines Schritt-

ten wurden in unserer Kohorte atypisches, nicht-isth-

machers in 0,65% aller Fälle, ein Hämatom in 0,3% und

musabhängiges Vorhofflattern (4,0%) und die atypische

ein Perikarderguss in 0,2% der Ablationsbehandlungen.

CARDIOVASCULAR MEDICINE – KARDIOVASKULÄRE MEDIZIN – MÉDECINE CARDIOVASCULAIRE

2016;19(9):231–236

ORIGINAL ARTICLE

236

In der spanischen Registerstudie [8] wurden die Kom-

nach sich zog, trat im Rahmen einer Ablation eines

plikationsraten noch differenzierter analysiert. Die

linksseitigen WPW auf. Bei einem Patienten kam es

meisten Komplikationen traten hier bei der Ablation

nach Ablation eines isthmusabhängigen Vorhofflat-

von atypischem Vorhofflattern bzw. intraatrialen

terns zu einem relevanten Hämatom in der Leiste (1,5%

Reentry-Tachykardien auf. Von insgesamt 227 Ablati-

der typischen VHFla- bzw. 0,3% aller SVT-Ablationen).

onsbehandlungen kam es bei 5 Patienten zu einer rele-

Lungenembolien, kardiale Dekompensationen, Herz-

vanten Komplikation (2-mal Perikardtamponade, ein-

infarkte oder Schlaganfälle sowie periinterventionelle

mal kompletter AV-Block, einmal Gefässkomplikation

Todesfälle traten in unserer Studienpopulation nicht

und einmal akutes Lungenödem). Von insgesamt 333

auf.

Ablationsbehandlungen fokaler atrialer Tachykardien traten bei 2,1% nennenswerte Komplikation auf, wobei 4 Patienten einen Perikarderguss entwickelten, zwei

Schlussfolgerung

vaskuläre Komplikationen aufwiesen und bei einem

Die Radiofrequenzablation hat sich für supraventriku-

aufgrund eines AV-Blocks ein Schrittmacher implan-

läre Tachykardien als äusserst erfolgreiches Behand-

tiert wurde. Die dritthäufigste Komplikationsrate lag

lungsverfahren etabliert. Sie stellt für viele dieser

mit 1% (n = 25 von 2 485) bei typischem Vorhofflattern

Rhythmusstörungen heutzutage die Therapie der Wahl

vor. Zwei Patienten erlitten einen Schlaganfall, bei

dar, zumal sie in vielen Fällen zu einer definitiven

einem erfolgte aufgrund eines AV-Blocks eine Schritt-

Heilung führt.

macher-Implantation und bei je einem Patienten kam

Die Häufigkeitsverteilung supraventrikulärer Tachy-

es zur Entwicklung eines Perikardergusses, zu einer

kardien, der akute Ablationserfolg sowie die hiermit

kardialen Dekompensation und zu einer Lungenembo-

assoziierten Komplikationsraten sind in unserer Stu-

lie. In dieser Gruppe waren zwei Todesfälle (Stroke und

die an einem tertiären Schweizer Zentrum weitgehend

kardiogener Schock) zu verzeichnen. Von den 1 999 Pa-

vergleichbar mit den internationalen Erfahrungen.

tienten, bei denen eine zusätzliche akzessorische Bahn

Die Komplikationsrate ist insgesamt sehr gering, wes-

(WPW) abladiert wurde, entwickelten 1,4% eine rele-

wegen die Ablation bei einer Vielzahl der Patienten

vante Komplikation mit 15 Gefässkomplikationen,

ambulant durchgeführt werden kann.

4 Schrittmacher-Implantationen infolge eines AVBlocks, 3 Schlaganfällen, 4 Herzinfarkten und 2 Peri-

Disclosure statement

kardergüssen. Die geringste Komplikationsrate mit

Die Autoren erhielten Forschungs- und Educational Grants für ihre Institution von Bayer Healthcare, Biosense Webster, Biotronik, Boston Scientific, Daiichi Sankyo, Medtronic, Actelion und St. Jude Medical. Thomas F. Lüscher: Beratungs- und/oder Vortragshonorare von AstraZeneca, Bayer Healthcare, Daiichi Sankyo und Medtronic. Jan Steffel: Beratungs- und/oder Vortragshonorare von Amgen, AstraZeneca, Atricure, Bayer, Biosense Webster, Biotronik, Boehringer-Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cook Medical, Daiichi Sankyo, Medtronic, Novartis, Pfizer, Roche, Sanofi-Aventis, Sorin, St. Jude Medical und Zoll. Dr. Steffel ist Co-Director von CorXL. Alexander Breitenstein: Educational Grants von Biotronik, Biosense Webster und Actelion. Ardan M. Saguner: Vortragshonorar und Reiseunterstützung für wissenschaftliche Kongresse von Boston Scientific, Cambridge, MA und Biosense Webster, Diamond Bar, CA. Laurent Haegeli: Beratungs- und Vortragshonorare von St. Jude Medical. Die übrigen Autoren erklären keine potentiellen Interessenskonflikte.

0,6% (n = 17 von 2 842) wurden bei Ablationsbehandlungen von AVNRTs beobachtet, wobei bei 0,35% aufgrund eines AV-Blocks eine Schrittmacher-Implantation erforderlich wurde, bei 6 eine Gefässkomplikation und bei einem eine Lungenembolie auftrat. Unsere Komplikationsraten waren mit 1,1% ähnlich tief wie in den genannten Studien. In 2 Fällen (1,1% der Korrespondenz:

AVNRT-Ablationen) kam es zu einem kompletten AV-

PD Dr. med. Jan Steffel

Block im Rahmen einer Ablation des slow pathways bei

Leitender Arzt Kardiologie

(typischer und atypischer) AVNRT wobei nur in einem

Co-Leiter Rhythmologie Universitäres Herzzentrum Zürich Rämistrasse 100 CH-8091 Zürich j.steffel[at]gmx.ch

Fall eine Schrittmacher-Implantation erforderlich wurde (0,54% der AVNRT- bzw. 0,29% aller SVT-Ablationen). Ein hämodynamisch nicht relevanter Perikarderguss, welcher keine therapeutischen Konsequenzen

CARDIOVASCULAR MEDICINE – KARDIOVASKULÄRE MEDIZIN – MÉDECINE CARDIOVASCULAIRE

Referenzen Die vollständige Literaturliste finden Sie in der Online-Version des Artikels unter www.cardiovascmed.ch.

2016;19(9):231–236

CASE REPORT

237

What to do with a redundant pacemaker...

To explant, or not to explant, that is the question Simon von Gunten, Jean-Luc Crevoisier, Michael Kühne, Tobias Reichlin, Stefan Osswald, Christian Sticherling, Beat Schaer

Summary Recurrent surgery in device patients carries a certain risk of infection and should therefore be kept to a minimum. We present the case of a patient in whom a new pacemaker had to be implanted from the left side and the question was, what should be done with the redundant pacemaker on the right side: to explant or not to explant? The answer depends upon the behaviour of the pacemaker at the time of elective replacement indication (ERI) and of end of life (EOL), and dif fers between the five manufacturers operating in Switzerland. This behaviour is explained in detail and thus can guide cardiologists towards individual decision making. Key words: pacemaker; replacement; end of life; end of service

Figure 1: Chest X ray at presentation.

Case presentation In 1991, a 65-year-old male patient was implanted with

an ODO or OOO mode, or if it should be explanted.

a dual chamber pacemaker for symptomatic persistent

Arguments against explanting the pacemaker were

third degree atrioventricular block. Both leads were

that there was no obvious clinical need and that there

inserted via the right cephalic vein. Elective device re-

is a statistical 1.4% chance of infection [1], double that

placement was first necessary in 2000. In 2007, the bat-

associated with a de-novo implant [2]. This had to be

tery was depleted again. As an insulation defect of the

balanced against possible interferences between the

atrial lead was present, lead replacement was planned

new pacemaker implanted from the left side and the

at the same time. During surgery, the subclavian vein

old device falling below the “elective replacement

was found to be occluded, resulting in the implant-

indicator” (ERI) and then later going into its “end of

ation of a new atrial lead via the right internal jugular

life” (EOL) mode.

vein. In March 2015, the pacemaker battery was once

If the pacing mode remains in ODO or OOO mode, no

more depleted. As the right ventricular lead now

problems will occur. However, if the mode switched to

showed a slow, but continuous decrease in impedance

VOO or DOO, induction of ventricular fibrillation via

(from 510 ohms in 2007 to 330 ohms in 2015), the pa-

an “R on T phenomenon” is possible. Albeit rare [3], this

tient was offered implantation of a new dual chamber

is an avoidable life-threatening complication. If the

pacemaker from the left side. Extraction of the leads

pacemaker switches to a VVI or DDD mode with a fixed

was not considered for various reasons (age, comorbid-

rate, this fear is unfounded, but the fixed rate might

ities and access to one lead via the jugular vein). The pa-

limit programming of the new device. A final option

tient did not express discomfort from the right-sided

would be to program the output to its lowest and pulse

old device (fig. 1).

width to its shortest value. Depending on the manufacturer, different behaviours

Pacemaker problem

at EOL are present. They are presented in alphabetical

The pertinent question was whether the right-sided

order in table 1.

pacemaker should be left in place and programmed to

CARDIOVASCULAR MEDICINE – KARDIOVASKULÄRE MEDIZIN – MÉDECINE CARDIOVASCULAIRE

2016;19(9):237–238

CASE REPORT

238

mode was. Sensing is set to 2.2 mV in a unipolar mode.

Table 1: Necessity of pacemaker explantation for different manufacturers.

Even if a OOO mode were reprogrammed, the next day

Manufacturer

Recommendation

ment and switch back to VVI 70/min. This interferes

Biotronik

no explantation

Boston Scientific

no explantation

Medtronic

explantation

Sorin

explantation

St Jude Medical

explantation

the device will again perform an impedance measurewith standard settings, especially in patients with DDD pacemakers. This behaviour applies to pacemakers of all generations as well as to CRT devices. The pacemaker thus usually needs to be explanted.

St Jude Medical pacemakers Biotronik pacemakers

The programmed pacemaker mode is not affected and

The pacemaker can be programmed to an “off” mode.

remains in the ODO/OVO setting. However, if the pace-

However, a password given by the manufacturer’s repre-

maker falls into “back-up” mode, it switches into a VVI

sentative is needed to program this mode. At ERI, this

mode. Such a switch occurs when the pacemaker

“off” mode is not changed. Programming is only re-

notices inconsistencies in its software status. In spite

verted if a back-up mode event occurs, e.g., due to heavy

of this being a rare phenomenon, St Jude Medical

electromagnetic interference, or at “end of life”. How-

recommends explanting the pacemaker.

ever, at EOL pacing output is already so low that no

The pacemaker thus needs to be explanted.

effective pacing occurs. This behaviour applies to pacemakers of all generations as well as to cardiac resynchronisation therapy (CRT) devices.

Conclusion

The pacemaker thus does not need to be explanted.

In our patient, the Medtronic pacemaker was ex-

Boston Scientific pacemakers

the patient was uneventful.

Pacing can be programmed “off”. This mode is not

Generally, it depends on the specific behaviour of the

planted. Over a follow-up of 9 months, the course of

affected by EOL. During further depletion, the pace-

pacemakers from each manufacturer whether a pace-

maker will switch to a storage mode and then cannot

maker must be explanted or not in such a situation.

pace any longer. This behaviour applies to pacemakers of all generations as well as to CRT devices. The pacemaker thus does not need to be explanted.

Medtronic pacemakers At ERI, programming will switch to VVI 65/min with an output of 5.0 V / 1.0 ms. At EOL, the device typically continues to work in VVI 65/min. Sometimes beyond EOL (and there is no way to tell when) there is a moment when the device can reset (“power on reset”) owing to low battery voltage, and resume pacing at

Disclosure statement Simon von Gunten, Jean-Luc Crevoisier and Tobias Reichlin: none declared. Michael Kühne has served on the speakers’ bureau for Boston Scientific, St Jude Medical and Biotronik. Stefan Osswald has served on the speakers’ bureau for Medtronic, Boston Scientific, Biotronik, St Jude Medical and has received unrestricted grants from Medtronic, Boston Scientific, Biotronik, and St Jude Medical. Christian Sticherling has served on the speakers’ bureau for Medtronic, Biotronik and Sorin and had scientific support from Medtronic, Biotronik, Boston Scientific, St Jude Medical and Sorin. Beat Schaer has served on the speakers’ bureau for Medtronic and Boston Scientific.

random settings and device behaviour. This behaviour applies to pacemakers of all generations as well as to CRT devices.

References 1

The pacemaker thus needs to be explanted. Correspondence: Prof. Beat Schaer, MD University Hospital Department of Cardiology Petersgraben 4 CH-4031 Basel beat.schaer[at]usb.ch

Sorin (LivaNova) pacemakers

2

If the battery impedance falls below the ERI value, the device switches to VVI 70/min with unipolar pacing of 5.0 V / 0.5 ms, whatever the previous programmed

CARDIOVASCULAR MEDICINE – KARDIOVASKULÄRE MEDIZIN – MÉDECINE CARDIOVASCULAIRE

3

Poole JE, Gleva MJ, Mela T, Chung MK, Uslan DZ, Borge R, et al. Complication Rates Associated With Pacemaker or Implantable Cardioverter-Defibrillator Generator Replacements and Upgrade Procedures Results From the REPLACE Registry. Circulation. 2010;122(16):1553–U43. Polyzos KA, Konstantelias AA, Falagas ME. Risk factors for cardiac implantable electronic device infection: a systematic review and meta-analysis. Europace. 2015;17(5):767–77. Oupadia P, Ramaswamy K. Images in clinical medicine. “R-on-T” phenomenon. N Engl J Med. 1998;338(25):1812.

2016;19(9):237–238

CASE REPORT

239

A simple method to identif y one cause of voltage loss on the ECG

A benign cause for voltage loss in the precordial leads Elefteri Buset, Richard Kobza, Florim Cuculi Heart Centre Lucerne, Luzerner Kantonsspital, Switzerland

the precordial leads but normal voltage in the peri-

Summary

pheral leads.

This case report describes a cause of precordial voltage loss with normal voltage in the peripheral leads in patients with obesity and/or temporal causes of increased intra-abdominal pressure. Important differential diagnoses were excluded with blood analyses, ECG and echocardiography. By placing the ECG-electrodes one or two intercostal spaces cranially we were able to detect the origin of the voltage loss. This case demonstrates that the standard position of the precordial ECG leads might not always correspond to the true anatomical position of the heart. If the probability of a cardiac or pericardial disease is excluded, this method might be sufficient as a basic diagnostic tool.

High-sensitivity troponin was slightly elevated at 0.024 µg/l (200 mm Hg. Physical examination was

ECG. By placing the precordial leads cranially the

normal and the ECG (fig. 1) demonstrated low voltage in

“modified” ECG returns to normal.

2

Figure 1A: Low voltage in the precordial leads with ECG electrodes positioned in the ordinary manner.

CARDIOVASCULAR MEDICINE – KARDIOVASKULÄRE MEDIZIN – MÉDECINE CARDIOVASCULAIRE

2016;19(9):239–240

CASE REPORT

240

Figure 2: By placing the precordial leads one intercostal space cranially the low voltage could be reduced.

Figure 3: By placing the precordial leads two intercostal spaces cranially the ECG normalised.

Importantly, alternative diagnoses that also lead to

pressure (ascites, laparoscopic procedures). We advise

low voltage need to be considered. Pericardial effusion

recording the ECG one and two intercostal spaces

leads to a voltage loss mainly in the peripheral, rather

cranially in order to differentiate the cause of voltage

than the precordial, leads and can be easily excluded

loss in these patients.

with transthoracic echocardiography. Cardiac amyloidCorrespondence:

osis leads to voltage loss in all leads and careful echo-

Dr. med. Elefteri Buset

cardiography usually helps to establish this diagnosis.

Heart Centre Lucerne,

This case describes a less known but not uncommon

Luzerner Kantonsspital CH-6000 Luzern 16 elefteri.buset[at]luks.ch

cause of precordial voltage loss in patients with obesity and/or temporal causes of increased intra-abdominal

CARDIOVASCULAR MEDICINE – KARDIOVASKULÄRE MEDIZIN – MÉDECINE CARDIOVASCULAIRE

Disclosure statement No financial support and no other potential conflict of interest relevant to this article was reported.

Reference 1

Cuculi F, Jamshidi P, Kobza R, Rohacek M, Erne P. Precordial low voltage in patients with ascites. Europace. 2008;10:96–8.

2016;19(9):239–240

CASE REPORT

241

New percutaneous ventricular assist device in a high-risk percutaneous conronary intervention

HeartMate PHP axial pump for high-risk PCI Diego Arroyo a,b , Serban Puricel b , Mario Togni b , Stéphane Cook b a b

Cardiothoracic and Vascular Intensive Care Unit, Auckland City Hospital, Auckland, NewZealand Department of Cardiology, University and Hospital Fribourg, Fribourg, Switzerland

[1]. To date, the most used pVAD in Switzerland is the

Summary

Impella LP 2.5 (Abiomed – Impella Cardiosystems AG;

Percutaneous left ventricular assist devices (pVADs) can provide temporary circulatory support during high-risk percutaneous coronary interventions (PCIs). We describe the first case in Switzerland of high-risk PCI with a new pVAD, the HeartMate PHP axial pump (St Jude Medical). Key words: coronary angioplasty; high-risk PCI; percutaneous ventricular assist device

Aachen, Germany) [2, 3]. The benefit of pVADs in cardiogenic shock, particularly interms of 30-day mortality, is uncertain [4]. The new HeartMate PHP is a nonpulsatile axial flow pump (St Jude Medical) that works on the principle of an Archimedes screw, driving blood from the left ventricle into the ascending aorta. The deployable ventriculoaortal conduit with a large impeller reaches a theoretical output of up to 4–5 l/min with

Introduction

typically 17 000–20 000 rotations per minute (rpm) (fig. 1).

Several percutaneous ventricular assist devices

We report the first clinical use of this device in Switzer-

(pVADs) have become clinically available for cardiac

land in March 2016, in a patient undergoing a high-risk

support either in cardiogenic shock or, prophylacti-

PCI.

cally, for percutaneous coronay interventions (PCIs) in patients at high-risk of haemodynamic deterioration

Case report An otherwise active and independent 86-year-old male with a history of poorly controlled hypertension consulted for progressive shortness of breath and typical angina Canadian Cardiovascular Society (CCS) class III. His ECG showed first degree atrioventricular block, a left anterior hemiblock and Q waves from V1–V4. There was left ventricular hypertrophy with severe systolic dysfunction (left ventricular ejection fratction [LVEF] 30%) and anterior wall hypokinesis, but no significant valvular disease on echocardiogram (left ventricular angiogram, fig. 2 panels E, F). The coronary angiogram revealed severe three-vessel coronary artery disease (fig. 2 panels A–D). There was a significant stenosis of the distal left main (Medina 1.1.1). The left anterior descending artery was suboccluded in the proximal and distal portion with numerous calcified and aneurysmal lesions. The proximal, middle and distal circumflex artery, as well as the mid portion of the right coro-

Figure 1: HeartMate PHP. The low profile 13 Fr catheter is introduced via percutaneous femoral arterial access. It is progressed on a guidewire across the aortic valve and then unsheathed to deploy the high-profile 24 Fr axial pump. The blood is aspirated from the left ventricle to the ascending aorta, thereby unloading the left ventricle while increasing the aortic and coronary pressures. Reprinted with the permission of Thoratec Corporation (St Jude Medical).

CARDIOVASCULAR MEDICINE – KARDIOVASKULÄRE MEDIZIN – MÉDECINE CARDIOVASCULAIRE

nary artery, had significant stenosis. The patient opted for an invasive approach after he had been thoroughly informed about the different treatment possibilities, including conservative medical management. Given the severity of the coronary artery disease, the procedure was deemed high risk and pVAD support was planned.

2016;19(9):241–244

CASE REPORT

242

Figure 2: Coronary angiograms (panels A–D) and left ventricular angiogram (panels E, F). Three-vessel coronary artery disease with subtotal distal left main (3) to proximal left anterior descending artery (LAD) stenosis (lesion 1), significant proximal (lesion 2) and distal (lesion 3) LAD stenosis, high grade ostial circumflex artery (LCx, lesion 4), and intermediate lesions from the mid portions of LCx and the right coronary artery (RCA). Left ventricular ejection fraction was severely depressed (panels E, F).

Figure 3: HeartMate-PHP implantation. Panel A: puncture of the left femoral artery under fluoroscopy. Panels B, C: Deployment of the HeartMate conduit by pulling out the covering sheath. Dashed line delineates the aortic valve.

After the patient had given written informed consent,

performed. Then, a 14 French (Fr) sheath was placed

the decision to perform a HeartMate-PHP-assisted PCI

into the descending aorta. Systemic anticoagulation

was made. Both groins were used for vascular access.

was achieved with administration of unfractionated

Following local anaesthesia, puncture of the left femo-

heparin (70 U/kg); the patient had been pretreated

ral artery under fluoroscopy (fig. 3 panel A) and preclo-

with acetylsalicylic acid 100 mg/day. A 5 Fr JR4 catheter

sure of the left femoral with two Perclose devices were

was positioned in the left ventricle and then exchanged

CARDIOVASCULAR MEDICINE – KARDIOVASKULÄRE MEDIZIN – MÉDECINE CARDIOVASCULAIRE

2016;19(9):241–244

CASE REPORT

243

over a 0.018 inch guidewire for the HeartMate-PHP

(fig. 3 panels B, C). Circulatory support was initiated at

catheter. The correct position of the device was verified

the minimum pump speed (approximately 1 l/min)

by fluoroscopy by using a 5 Fr pigtail catheter from the

and maintained throughout the intervention. Acti-

right femoral artery as a marker of the aortic valve and

vated clotting time was kept at 250 s.

the conduit was unsheathed up to its final 24 Fr size

Following this, the pigtail catheter was exchanged for a

Figure 4: Percutaneous coronary intervention. Panels A–C: The three (lesions 1–3) left main to proximal left anterior descending (LAD) were treated with balloon angioplasties and implantation of two drug-eluting stents. Panels D–F: ostial circumflex artery (LCx, lesion 4) was treated by implantation of a third drug-eluting stent and kissing-balloon inflation. Good final results (panels C, F).

Figure 5: HeartMate PHP re-sheath. Panels A, B: the conduit was easily re-sheathed into the catheter by pulling down the pump into the sheath. Panel C: tightening of the two Proglides completed haemostasis.

CARDIOVASCULAR MEDICINE – KARDIOVASKULÄRE MEDIZIN – MÉDECINE CARDIOVASCULAIRE

2016;19(9):241–244

CASE REPORT

244

6 Fr Q4 guiding catheter with PCI of the distal left ante-

The Impella CP® (also known as cVAD in Europe) (Abi-

rior descending artery (LAD) (SYNERGY II 2.25–20 mm,

omed – Impella Cardiosystems AG; Aachen, Germany)

Boston Scientific, fig. 4 panel B left) and proximal LAD

is another axial pump that achieves higher flows than

to distal left main artery (SYNERGY II 4.00–38 mm, Bos-

the Impella LP 2.5 while using the same 13 Fr insertion

ton Scientific, fig. 4 panel B right) with T-stenting into

sheath. The flow reaches 3.5 l/min at the cost of higher

the left circumflex artery (SYNERGY II 2.75–12 mm, Bos-

(up to 46 000) rpm. Presumed advantages of the Heart-

ton Scientific, fig. 4 panels B, E). Postdilatation with

Mate PHP over both Impella devices include a higher

kissing balloon inflation (4.00–15 mm in LAD, 2.75–12

antegrade flow mimicking physiological cardiac out-

mm in the left circumflex artery) demonstrated a good

put, and possibly lower risk of hemolysis given the

final angiographic result (fig. 4 panels C, F). During the

lower rpm. However, the higher 24 Fr profile could

intervention no significant haemodynamic changes

translate into more valvular complications. There is no

were noted, and the patient tolerated the balloon infla-

available data directly comparing Impella CP® to

tions well. The HeartMate-PHP was then gently re-

HeartMate PHP.

moved into the descending aorta. The pump was

Venoarterial extracorporeal life support (VA-ECLS)

stopped and the conduit could be easily resheathed

may also deliver the necessary support to both heart

into the catheter (fig. 5 panels A, B). Haemostasis was

and lungs during high-risk PCI. The system is a modi-

achieved with tightening of the two Perclose (fig. 5

fied cardiopulmonary bypass, providing higher non-

panel C) and the patient was given a loading dose of

pulsatile flows (up to 6 l/min) at lower rpm (up to 4500)

60 mg prasugrel.

and full lung support (oxygenation and CO2 removal) in cases of concomitant respiratory failure. The sys-

Discussion

Correspondence: Diego Arroyo, MD Cardiothoracic and Vascular

This first case shows the feasibility of implantating a

through a centrifugal pump, an oxygenator and heat

new pVAD for partial circulatory support during a

exchanger membrane, to return to the patient via a

high-risk percutaneous coronary intervention. The

17–21 Fr femoral arterial cannula. The high-profile can-

current evidence for the use of HeartMate PHP is very

nulas increase the risk of bleeding and ischaemia, and

limited. The first-in-human study in 10 patients with

if the system is kept in place for several hours, a distal

complex coronary disease and reduced left ventricular

reperfusion cannula in the superior femoral artery is

function showed good support during procedures and

mandatory. The perfusion is retrograde and there is a

no adverse events at 30 days [5]. The Shield I trial, which

concern of increased left ventricular afterload and

contributed to the CE approval, tested the device in 30

stress, and thus myocardial oxygen demand. Finally,

patients undergoing PCI. None had device-related car-

the cannula implantation and removal is more cum-

diac death, myocardial infarction or intraprocedural

bersome and the procedure usually requires the in-

hypotension, and the overall incidence of complica-

volvement of a highly trained multidisciplinary team,

tions related to HeartMate PHP was low [6]. The Shield

often including perfusionists. Although it does have a

II trial will aim to randomise 425 patients to either

crucial place in high-risk transcatheter aortic valve

HearMate PHP or Impella LP 2.5 for high-risk PCI [7].

implantation, its place in high-risk PCI is likely to be

Potential complications in cases of prolonged use are

limited to very specific cases, especially with the im-

haemolysis, limb ischaemia, vascular injury and bleed-

provement of axial pumps.

ing. The mid-term and long-term safety of the device

Clinical evidence in the years to come should provide

in terms of effects on the aortic valve remains

the necessary data to identify the needs, risks and

unknown. Classic contraindications are mechanical

benefits associated with these devices.

aortic valve, left ventricular thrombus and aortic dis-

Intensive Care Unit

section; aortic stenosis and regurgitation are relative

Auckland City Hospital

contraindications. One inconvenience of the Heart-

Park Road 4, Grafton NZ-Auckland 1140 da.arroyo[at]gmail.com

temic blood is drained via a 21–29 Fr femoral venous cannula placed in the inferior vena cava. It then passes

Mate PHP device noted by the operators was the noise from the motor of the impeller.

CARDIOVASCULAR MEDICINE – KARDIOVASKULÄRE MEDIZIN – MÉDECINE CARDIOVASCULAIRE

References The full list of references is included in the online article at www.cardiovascmed.ch

2016;19(9):241–244

THE INTERESTING ECG

245

An avoidable cause of life-threatening arrhythmia

A strange ECG Mirdita Gaxherri, Jürg Schläpfer Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland

Case presentation

later, the patient suddenly lost consciousness during a walk.

The 84-year-old patient, who lived abroad, was known

On site, a tachycardia of 135 bpm was documented with

to have ischaemic heart disease with an old postero-

haemodynamic instability, and the patient was admit-

basal transmural infarction. He had been treated for

ted to the emergency department. The ECG on arrival

12 months with oral verapamil for supraventricular

is shown in figure 1.

ectopic beats with left bundle-branch block. His cardiologist had recently changed his antiarrhythmic medication after documenting an increase in the prevalence of ectopic supraventricular beats. Two weeks

Question What can explain this arrhythmia?

Figure 1: The 12-lead ECG on admission.

Comment

antiarrhythmic drugs. The patient’s wife was able to inform the medical team that the medication intro-

The ECG on arrival in the emergency department

duced recently by the cardiologist was flecainide 2×

(fig. 1) shows a very wide QRS tachycardia, regular at

100 mg/day. Thus, the diagnosis was ventricular tachy-

130 bpm (QRS 200 ms; right axis deviation). The QRS

cardia due to a proarrhythmic effect of flecainide. The

complexes have an undefined aspect (neither right nor

laboratory results were not relevant.

left bundle branch morphology); QRS beginning and

The patient was cardioverted electrically and the ECG

end are difficult to pinpoint precisely (a sinusoidal-like

immediately thereafter shows atrial fibrillation with a

pattern); there is no visible P wave.

slow ventricular rate, a wide left bundle-branch block

Such large and deformed QRS complexes should first

(190 ms) and left axis deviation (fig. 2).

suggest either severe hyperkalaemia or the effects of

During the following days, the QRS progressively nar-

CARDIOVASCULAR MEDICINE – KARDIOVASKULÄRE MEDIZIN – MÉDECINE CARDIOVASCULAIRE

2016;19(9):245–246

THE INTERESTING ECG

246

Figure 2: ECG after electrical cardioversion.

rowed to 120 ms and the patient spontaneously cardio-

left ventricular function, ventricular scar tissue, too

verted to sinus rhythm. The investigations performed

high a dose and/or rapid dose increases are factors

thereafter showed no active myocardial ischaemia; the

associated with proarrhythmia risk. Premonitory

left ventricular ejection fraction was measured at 40%.

signs on ECG include excessive increases in QRS dura-

Our efforts to reassure the patient were ineffective: he

tion [2].

lost confidence and remained extremely anxious.

The CAST results rapidly led to a contraindication for

Despite his only moderate left ventricular dysfunction

the use of class Ic sodium channel blockers after myo-

the patient was finally fitted with a cardioverter-defi-

cardial infarction [4]. However, this warning was not

brillator.

respected in the present case, leading to a life-threat-

This case demonstrates once more the proarrhythmic

ening proarrythmic effect.

effect of flecainide in patients with ischaemic cardiopathy. Flecainide, a class 1c sodium channel blocker, re-

Disclosure statement

sults in significant rate- and dose-dependent slowing

No financial support and no other potential conflict of interest relevant to this article was reported.

of conduction, mainly in His–Purkinje and ventricular myocardial fibres and preferentially in ischaemic myocardium [1, 2]. On the ECG it prolongs the PR and QT in-

References

tervals and the QRS complex.

1

In 1989, the Cardiac Arrhythmia Suppression Trial (CAST) showed excess mortality or nonfatal cardiac ar-

2

rest rate among postmyocardial infarction patients Correspondence:

treated with encainide or flecainide, as compared with

Mirdita Gaxherri

placebo-treated patients [3]. Class 1c ventricular pro-

Centre Hospitalier Universitaire Vaudois (CHUV)

arrhythmic effects facilitate the induction of reentry

rue du brugnon 46

and can manifest as monomorphic sinusoidal wide

CH-1011 Lausanne mirdita.gaxherri[at] hotmail.com

QRS tachycardia (as in the present case), or as polymorphic ventricular tachycardia or fibrillation. Decreased

CARDIOVASCULAR MEDICINE – KARDIOVASKULÄRE MEDIZIN – MÉDECINE CARDIOVASCULAIRE

3

4

Brugada J, Boersma L, Kirchhof C, Allessie M. Proarrhythmic effects of flecainide. Experimental evidence for increased susceptibility to reentrant arrhythmias. Circulation. 1991;84:1808–18. Aliot E, Capucci A, Crijns HJ, Goette A, Tamargo J. Twenty-five years in the making: flecainide is safe and effective for the management of atrial fibrillation. Europace 2011;13:161–73. The Cardiac Arythmia Suppression Trial (CAST) Investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomised trial of arrhythmia suppression after myocardial infarction. N Engl J Med 1989;321:406–12. Priori SG, Blomstrom-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J. 2015;36:2793–867.

2016;19(9):245–246