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