****Risk Stratification for PrimaryImplantation of a
Cardioverter-Defibrillator inPatients With Ischemic Left
Ventricular DysfunctionIlan Goldenberg, MD,* Anant K. Vyas, MD,
MPH, W. Jackson Hall, PHD, Arthur J. Moss, MD,*Hongyue Wang, PHD,
Hua He, MA, Wojciech Zareba, MD, PHD,* Scott McNitt, MS,*Mark L.
Andrews, BBA,* for the MADIT-II InvestigatorsRochester and Buffalo,
New YorkObjectives The study was designed to develop a simple risk
stratification score for primary therapy with an
implantablecardioverter-defibrillator (ICD).Background Current
guidelines recommend primary ICD therapy in patients with a low
ejection fraction (EF). However, thebenefit of the ICD in the low
EF population may not be uniform.Methods Best-subset
proportional-hazards regression analysis was used to develop a
simple clinical risk score for the endpoint of all-cause mortality
in patients allocated to the conventional therapy arm of MADIT
(Multicenter AutomaticDefibrillator Implantation Trial)-II after
excluding a pre-specified subgroup of very high-risk (VHR)
patients(defined by blood urea nitrogen [BUN] 50 mg/dl and/or serum
creatinine 2.5 mg/dl). The benefit of the ICDwas then assessed
within risk score categories and separately in VHR patients.Results
The selected risk score model comprised 5 clinical factors (New
York Heart Association functional class II, age70 years, BUN 26
mg/dl, QRS duration 0.12 s, and atrial fibrillation). Crude
mortality rates in the conventionalgroup were 8% and 28% in
patients with 0 and 1 risk factors, respectively, and 43% in VHR
patients.Defibrillator therapy was associated with a 49% reduction
in the risk of death (p 0.001) among patients with1 risk factors (n
786), whereas no ICD benefit was identified in patients with 0 risk
factors (n 345; hazardratio 0.96; p 0.91) and in VHR patients (n
60; hazard ratio 1.00; p 0.99).Conclusions Our data suggest a
U-shaped pattern for ICD efficacy in the low-EF population, with
pronounced benefit inintermediate-risk patients and attenuated
efficacy in lower- and higher-risk subsets. (J Am Coll Cardiol
2008;51:28896) 2008 by the American College of Cardiology
Foundation*Risk Stratification for PrimaryImplantation of a
Cardioverter-Defibrillator inPatients With Ischemic Left
Ventricular DysfunctionIlan Goldenberg, MD,* Anant K. Vyas, MD,
MPH, W. Jackson Hall, PHD, Arthur J. Moss, MD,*Hongyue Wang, PHD,
Hua He, MA, Wojciech Zareba, MD, PHD,* Scott McNitt, MS,*Mark L.
Andrews, BBA,* for the MADIT-II InvestigatorsRochester and Buffalo,
New YorkObjectives The study was designed to develop a simple risk
stratification score for primary therapy with an
implantablecardioverter-defibrillator (ICD).Background Current
guidelines recommend primary ICD therapy in patients with a low
ejection fraction (EF). However, thebenefit of the ICD in the low
EF population may not be uniform.Methods Best-subset
proportional-hazards regression analysis was used to develop a
simple clinical risk score for the endpoint of all-cause mortality
in patients allocated to the conventional therapy arm of MADIT
(Multicenter AutomaticDefibrillator Implantation Trial)-II after
excluding a pre-specified subgroup of very high-risk (VHR)
patients(defined by blood urea nitrogen [BUN] 50 mg/dl and/or serum
creatinine 2.5 mg/dl). The benefit of the ICDwas then assessed
within risk score categories and separately in VHR patients.Results
The selected risk score model comprised 5 clinical factors (New
York Heart Association functional class II, age70 years, BUN 26
mg/dl, QRS duration 0.12 s, and atrial fibrillation). Crude
mortality rates in the conventionalgroup were 8% and 28% in
patients with 0 and 1 risk factors, respectively, and 43% in VHR
patients.Defibrillator therapy was associated with a 49% reduction
in the risk of death (p 0.001) among patients with1 risk factors (n
786), whereas no ICD benefit was identified in patients with 0 risk
factors (n 345; hazardratio 0.96; p 0.91) and in VHR patients (n
60; hazard ratio 1.00; p 0.99).Conclusions Our data suggest a
U-shaped pattern for ICD efficacy in the low-EF population, with
pronounced benefit inintermediate-risk patients and attenuated
efficacy in lower- and higher-risk subsets. (J Am Coll Cardiol
2008;51:28896) 2008 by the American College of Cardiology
Foundation*Risk Stratification for PrimaryImplantation of a
Cardioverter-Defibrillator inPatients With Ischemic Left
Ventricular DysfunctionIlan Goldenberg, MD,* Anant K. Vyas, MD,
MPH, W. Jackson Hall, PHD, Arthur J. Moss, MD,*Hongyue Wang, PHD,
Hua He, MA, Wojciech Zareba, MD, PHD,* Scott McNitt, MS,*Mark L.
Andrews, BBA,* for the MADIT-II InvestigatorsRochester and Buffalo,
New YorkObjectives The study was designed to develop a simple risk
stratification score for primary therapy with an
implantablecardioverter-defibrillator (ICD).Background Current
guidelines recommend primary ICD therapy in patients with a low
ejection fraction (EF). However, thebenefit of the ICD in the low
EF population may not be uniform.Methods Best-subset
proportional-hazards regression analysis was used to develop a
simple clinical risk score for the endpoint of all-cause mortality
in patients allocated to the conventional therapy arm of MADIT
(Multicenter AutomaticDefibrillator Implantation Trial)-II after
excluding a pre-specified subgroup of very high-risk (VHR)
patients(defined by blood urea nitrogen [BUN] 50 mg/dl and/or serum
creatinine 2.5 mg/dl). The benefit of the ICDwas then assessed
within risk score categories and separately in VHR patients.Results
The selected risk score model comprised 5 clinical factors (New
York Heart Association functional class II, age70 years, BUN 26
mg/dl, QRS duration 0.12 s, and atrial fibrillation). Crude
mortality rates in the conventionalgroup were 8% and 28% in
patients with 0 and 1 risk factors, respectively, and 43% in VHR
patients.Defibrillator therapy was associated with a 49% reduction
in the risk of death (p 0.001) among patients with1 risk factors (n
786), whereas no ICD benefit was identified in patients with 0 risk
factors (n 345; hazardratio 0.96; p 0.91) and in VHR patients (n
60; hazard ratio 1.00; p 0.99).Conclusions Our data suggest a
U-shaped pattern for ICD efficacy in the low-EF population, with
pronounced benefit inintermediate-risk patients and attenuated
efficacy in lower- and higher-risk subsets. (J Am Coll Cardiol
2008;51:28896) 2008 by the American College of Cardiology
Foundation*Risk Stratification for PrimaryImplantation of a
Cardioverter-Defibrillator inPatients With Ischemic Left
Ventricular DysfunctionIlan Goldenberg, MD,* Anant K. Vyas, MD,
MPH, W. Jackson Hall, PHD, Arthur J. Moss, MD,*Hongyue Wang, PHD,
Hua He, MA, Wojciech Zareba, MD, PHD,* Scott McNitt, MS,*Mark L.
Andrews, BBA,* for the MADIT-II InvestigatorsRochester and Buffalo,
New YorkObjectives The study was designed to develop a simple risk
stratification score for primary therapy with an
implantablecardioverter-defibrillator (ICD).Background Current
guidelines recommend primary ICD therapy in patients with a low
ejection fraction (EF). However, thebenefit of the ICD in the low
EF population may not be uniform.Methods Best-subset
proportional-hazards regression analysis was used to develop a
simple clinical risk score for the endpoint of all-cause mortality
in patients allocated to the conventional therapy arm of MADIT
(Multicenter AutomaticDefibrillator Implantation Trial)-II after
excluding a pre-specified subgroup of very high-risk (VHR)
patients(defined by blood urea nitrogen [BUN] 50 mg/dl and/or serum
creatinine 2.5 mg/dl). The benefit of the ICDwas then assessed
within risk score categories and separately in VHR patients.Results
The selected risk score model comprised 5 clinical factors (New
York Heart Association functional class II, age70 years, BUN 26
mg/dl, QRS duration 0.12 s, and atrial fibrillation). Crude
mortality rates in the conventionalgroup were 8% and 28% in
patients with 0 and 1 risk factors, respectively, and 43% in VHR
patients.Defibrillator therapy was associated with a 49% reduction
in the risk of death (p 0.001) among patients with1 risk factors (n
786), whereas no ICD benefit was identified in patients with 0 risk
factors (n 345; hazardratio 0.96; p 0.91) and in VHR patients (n
60; hazard ratio 1.00; p 0.99).Conclusions Our data suggest a
U-shaped pattern for ICD efficacy in the low-EF population, with
pronounced benefit inintermediate-risk patients and attenuated
efficacy in lower- and higher-risk subsets. (J Am Coll Cardiol
2008;51:28896) 2008 by the American College of Cardiology
Foundation*Could it be that easy? Clinical-risk score may further
stratify low-LVEF ICD candidates January 14, 2008 Steve
StilesWashington, DC - From a clinical trial largely responsible
for the current wave of primary-prevention ICD use comes a simple
clinical-risk scoring system that could potentially screen out
patients unlikely ever to need the devices [1]. The system is based
on five familiar criteria that, taken together, retrospectively
stratified control patients from the Multicenter Automatic
Defibrillator Implantation Trial (MADIT-2) trial for very high and
very low mortality risk. Famously in that study, which pitted
LVEF-driven ICD therapy against conventional management in the
post-MI setting, device therapy cut all-cause mortality by 31% over
a mean of 20 months [2]. "Our findings suggest that a simple
clinical risk score that includes age, heart-failure functional
class, [blood urea nitrogen] BUN levels, QRS duration, and the
presence of atrial fibrillation can delineate lower- and
higher-risk subsets in the low-EF population that correlate with
ICD efficacy," write Dr Ilan Goldenberg (University of Rochester
Medical Center, NY) and colleagues. The scoring system "clearly
distinguishes between very low risk patients without any clinical
risk factors, in whom an ICD cannot be expected to lower an already
very low mortality, and patients with one or more risk factors, in
whom the benefit of an ICD becomes more significant," Goldenberg
told heartwire. The analysis also found that ICD therapy's impact
on survival was significant among patients at intermediate risk,
those with one or two risk factors, but was minimal among those
with either none or at least three of the risk factors. There was
also no detectable benefit in a subgroup considered "very high
risk" (VHR) based solely on poor renal function. "Our data strongly
indicate a U-shaped benefit for ICD therapy, with lower efficacy in
low- and very-high-risk patients," Goldenberg said.The group's
report was published online January 14, 2008 by the Journal of the
American College of Cardiology and is scheduled for the journal's
January 22 issue. It appears that patients with advanced renal
failure and additional comorbiditieshave a very high rate of
nonarrhythmic death, possibly due to pump failure, organ failure,
or infection,for which an ICD is not helpful. In an accompanying
editorial [3], Dr Suneet Mittal (St Luke's-Roosevelt Hospital
Center, New York, NY) points out that while certain specialized
markers based on the electrocardiogramsuch as T-wave alternans,
heart-rate variability, and the signal-averaged ECGmay further risk
stratify MADIT-2-like patients for sudden death, perhaps the job
can be done effectively by the five markers identified by
Goldenberg et al, which are "readily obtainable in an in-office
setting."Both Mittal and Goldenberg emphasize that the findings
would have to be confirmed in large, prospective trials before they
could be used to further risk-stratify low-LVEF patients for device
therapy. For the retrospective analysis, the MADIT-2 population
(with prior MI and an LVEF 50 mg/dL and/or serum creatinine >2.5
mg/dL, and a non-VHR group (n=1131). Their absolute mortalities
over the course of the trial were 48% and 16%, respectively.
Two-year mortality solely in the VHR group was about 50% overall
and about the same for the 37 patients who had been assigned to ICD
therapy and the 23 in the conventional-therapy group; the adjusted
hazard ratio for mortality in the ICD recipients compared with
controls was an even 1.00 (p>0.99).The primary mode of death
among the conventionally treated VHR patients was "nonsudden,"
Goldenberg said. "Therefore, it appears that patients with advanced
renal failure and additional comorbiditieshave a very high rate of
nonarrhythmic death, possibly due to pump failure, organ failure,
or infection,for which an ICD is not helpful."Turning to MADIT-2's
non-VHR population, the scoring system was constructed from
prespecified risk factors that emerged as significantly and
independently predictive of mortality in multivariate analysis of
the 467 control patients: NYHA class 3 or 4, atrial fibrillation, a
QRS interval >120 ms, age older than 70 years, and BUN >26
mg/dL and 120 ms, age > 70 years, and BUN >26 mg/dL To
download table as a slide, click on slide logo below Patients
without any of the risk factors, Goldenberg said, "need to be
continually assessed, since these risk factors are time-dependent
and can change, and patients can acquire risk factors during
follow-up that might make them better candidates for ICD
implantation." MADIT-2 was funded by Guidant, now part of Boston
Scientific. Mittal reports receiving honoraria for speaking from
Boston Scientific, Medtronic, and St Jude Medical and fellowship
support from Boston Scientific and Medtronic. Sources Goldenberg I,
Vyas AK, Hall WJ, et al. Risk stratification for primary
implantation of a cardioverter-defibrillator in patients with
ischemic left ventricular dysfunction. J Am Coll Cardiol
2008:51:288-296. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic
implantation of a defibrillator in patients with myocardial
infarction and reduced ejection fraction. N Engl J Med 2002;
346:877-883. Mittal S. Selecting patients for an implantable
cardioverter-defibrillator. Can the genie be put back into the
bottle? J Am Coll Cardiol 2008:51:297-298.
*Prevalence and prognostic implications of
non-sustainedventricular tachycardia in ST-segment
elevationmyocardial infarction after revascularization witheither
fibrinolysis or primary angioplastyDan Eik Hfsten1*, Kristian
Wachtell3, Birgit Lund2, Henning Mlgaard2,and Kenneth Egstrup1on
behalf of the DANAMI-2 Investigators1Department of Medical
Research, Svendborg Hospital, 5700 Svendborg, Denmark; 2Department
of Cardiology, SkejbySygehus, A rhus University Hospital, A rhus,
Denmark; and 3Department of Cardiology, Rigshospitalet, Copenhagen,
DenmarkReceived 6 July 2006; revised 19 December 2006; accepted 21
December 2006; online publish-ahead-of-print 16 January 2007Aims We
compared the prevalence and prognostic implications of
non-sustained ventricular tachycardia(nsVT) detected early after
ST-segment elevation myocardial infarction (STEMI) in patients
randomizedto either fibrinolysis or primary angioplasty in the
DANAMI-2 trial.Methods and results Holter recordings were available
in 1017 patients (fibrinolysis: n 501; primaryangioplasty: n 516).
Primary endpoint was all-cause mortality. The prevalence of nsVT
was 8.8% infibrinolysis-treated, and 8.1% in primary
angioplasty-treated patients (P 0.71). During 4519 patientyearsof
follow-up (median 4.3 years), 116 patients died [fibrinolysis vs.
angioplasty: HR 1.1 (95%CI, 0.81.6), P 0.47]. In univariate
analysis, nsVT patients treated with fibrinolysis, had
significantlyhigher mortality when compared with those without nsVT
(P , 0.001). However, after adjustment forother relevant
prespecified risk factors, the association between nsVTand
mortality did not remain statisticallysignificant. In patients
treated with primary angioplasty, nsVTwas not associated with
mortalityin either univariate or multivariate analyses.Conclusion
Immediate revascularization with primary angioplasty for STEMI does
not affect the subsequentprevalence of nsVT when compared with
fibrinolysis. After adjustment for other relevant riskfactors, the
prognostic value of nsVT detected early after STEMI is limited,
regardless of the chosenreperfusion strategy.*Predictive Value of
Microvolt T-Wave Alternans forSudden Cardiac Death in Patients With
PreservedCardiac Function After Acute Myocardial InfarctionResults
of a Collaborative Cohort StudyTakanori Ikeda, MD, FACC,* Hideaki
Yoshino, MD,* Kaoru Sugi, MD, Kaoru Tanno, MD,Hiroki Shimizu, MD,
Jun Watanabe, MD, Yuji Kasamaki, MD, Akihiro Yoshida, MD#Takao
Kato, MD**Tokyo, Nishinomiya, Sendai, and Kobe, JapanOBJECTIVES We
conducted a collaborative cohort study to evaluate the predictive
power of microvoltT-wave alternans (TWA) in patients with preserved
left ventricular ejection fraction (LVEF)after myocardial
infarction (MI).BACKGROUND There is little information available
about the prognostic value of risk stratification markersin this
population. Although these patients have a relatively good
prognosis, identifyinghigh-risk patients is important in clinical
practice.METHODS This study enrolled 1,041 post-MI patients with an
LVEF 40% (average 55 10%).Microvolt TWA testing was performed 48 66
days after acute MI, and 10 other riskvariables were also
evaluated. The end points were prospectively defined as sudden
cardiacdeath or life-threatening arrhythmic events.RESULTS During a
follow-up of 32 14 months, 38 patients (3.7%) died of nonarrhythmic
causes andwere not considered for analysis. Of the 1,003 evaluable
patients, 18 (1.8%) reached an endpoint. Microvolt TWA was positive
in 169 patients (17%), negative in 747 (74%), andindeterminate in
87 (9%). A positive microvolt TWA test, nonsustained
ventriculartachycardia, and ventricular late potentials were
predictors of events, and percutaneouscoronary intervention
decreased the risk rate. On multivariate analysis, a positive
microvoltTWA test was the most significant predictor, with a hazard
ratio of 19.7 (p 0.0001). Thismarker had the highest sensitivity
and negative predictive value for events.CONCLUSIONS In patients
with preserved cardiac function, the incidence of indeterminate
results ofmicrovolt TWA is low, and a positive test result is
associated with arrhythmic events.Microvolt TWA could be used for
risk stratification in this low-risk population. (J Am CollCardiol
2006;48:2268 74) 2006 by the American College of Cardiology
Foundation*Predictive Value of Microvolt T-Wave Alternans forSudden
Cardiac Death in Patients With PreservedCardiac Function After
Acute Myocardial InfarctionResults of a Collaborative Cohort
StudyTakanori Ikeda, MD, FACC,* Hideaki Yoshino, MD,* Kaoru Sugi,
MD, Kaoru Tanno, MD,Hiroki Shimizu, MD, Jun Watanabe, MD, Yuji
Kasamaki, MD, Akihiro Yoshida, MD#Takao Kato, MD**Tokyo,
Nishinomiya, Sendai, and Kobe, JapanOBJECTIVES We conducted a
collaborative cohort study to evaluate the predictive power of
microvoltT-wave alternans (TWA) in patients with preserved left
ventricular ejection fraction (LVEF)after myocardial infarction
(MI).BACKGROUND There is little information available about the
prognostic value of risk stratification markersin this population.
Although these patients have a relatively good prognosis,
identifyinghigh-risk patients is important in clinical
practice.METHODS This study enrolled 1,041 post-MI patients with an
LVEF 40% (average 55 10%).Microvolt TWA testing was performed 48 66
days after acute MI, and 10 other riskvariables were also
evaluated. The end points were prospectively defined as sudden
cardiacdeath or life-threatening arrhythmic events.RESULTS During a
follow-up of 32 14 months, 38 patients (3.7%) died of nonarrhythmic
causes andwere not considered for analysis. Of the 1,003 evaluable
patients, 18 (1.8%) reached an endpoint. Microvolt TWA was positive
in 169 patients (17%), negative in 747 (74%), andindeterminate in
87 (9%). A positive microvolt TWA test, nonsustained
ventriculartachycardia, and ventricular late potentials were
predictors of events, and percutaneouscoronary intervention
decreased the risk rate. On multivariate analysis, a positive
microvoltTWA test was the most significant predictor, with a hazard
ratio of 19.7 (p 0.0001). Thismarker had the highest sensitivity
and negative predictive value for events.CONCLUSIONS In patients
with preserved cardiac function, the incidence of indeterminate
results ofmicrovolt TWA is low, and a positive test result is
associated with arrhythmic events.Microvolt TWA could be used for
risk stratification in this low-risk population. (J Am CollCardiol
2006;48:2268 74) 2006 by the American College of Cardiology
Foundation*Prognostic Value of T-Wave Alternans in PatientsWith
Heart Failure Due to Nonischemic CardiomyopathyResults of the ALPHA
StudyJorge A. Salerno-Uriarte, MD,* Gaetano M. De Ferrari, MD,
Catherine Klersy, MD,Roberto F. E. Pedretti, MD, Massimo Tritto,
MD, Luciano Sallusti, BS, Luigi Libero, MD,#Giacinto Pettinati,
MD,** Giulio Molon, MD, Antonio Curnis, MD, Eraldo Occhetta,
MD,Fabrizio Morandi, MD,* Paolo Ferrero, MD,# Francesco Accardi,
BS, for the ALPHA StudyGroup InvestigatorsVarese, Pavia, Tradate,
Castellanza, Milano, Torino, Casarano, Negrar, Brescia, and Novara,
ItalyObjectives The aim of this study was to assess the prognostic
value of T-wave alternans (TWA) in New York Heart Association(NYHA)
functional class II/III patients with nonischemic cardiomyopathy
and left ventricular ejection fraction(LVEF) 40%.Background There
is a strong need to identify reliable risk stratifiers among heart
failure candidates for implantablecardioverter-defibrillator (ICD)
prophylaxis. T-wave alternans may identify low-risk subjects among
post-myocardialinfarction patients with depressed LVEF, but its
predictive role in nonischemic cardiomyopathy is unclear.Methods
Four hundred forty-six patients were enrolled and followed up for
18 to 24 months. The primary end point wasthe combination of
cardiac death life-threatening arrhythmias; secondary end points
were total mortality andthe combination of arrhythmic death
life-threatening arrhythmias.Results Patients with abnormal TWA
(65%) compared with normal TWA (35%) tests were older (60 13 years
vs. 57 12 years), were more frequently in NYHA functional class III
(22% vs. 19%), and had a modestly lower LVEF (29 7% vs. 31 7%).
Primary end point rates in patients with abnormal and normal TWA
tests were 6.5% (95%confidence interval [CI] 4.5% to 9.4%) and 1.6%
(95% CI 0.6% to 4.4%), respectively. Unadjusted and adjustedhazard
ratios were 4.0 (95% CI 1.4% to 11.4%; p 0.002) and 3.2 (95% CI
1.1% to 9.2%; p 0.013), respectively.Hazard ratios for total
mortality and for arrhythmic death life-threatening arrhythmias
were 4.6 (p 0.002) and 5.5 (p 0.004), respectively; 18-month
negative predictive values for the 3 end points ranged between97.3%
and 98.6%.Conclusions Among NYHA functional class II/III
nonischemic cardiomyopathy patients, an abnormal TWA test is
associatedwith a 4-fold higher risk of cardiac death and
life-threatening arrhythmias. Patients with normal TWA tests havea
very good prognosis and are likely to benefit little from ICD
therapy. (J Am Coll Cardiol 2007;50:1896904) 2007 by the American
College of Cardiology Foundation***Ventricular
RepolarizationDynamicity Provides Independent PrognosticInformation
Toward Major Arrhythmic Eventsin Patients With Idiopathic Dilated
CardiomyopathyMassimo Iacoviello, MD, PHD,* Cinzia Forleo, MD,
PHD,* Pietro Guida, PHD,*Roberta Romito, MD, Antonio Sorgente, MD,*
Sandro Sorrentino, PHD,* Silvana Catucci, MD,*Filippo Mastropasqua,
MD, Mariavittoria Pitzalis, MD, PHDBari and Cassano delle Murge,
Italy; and Greenville, North CarolinaObjectives The purpose of this
work was to evaluate whether ventricular repolarization dynamicity
predicts major arrhythmicevents in patients with idiopathic dilated
cardiomyopathy (DCM).Background Arrhythmic risk stratification in
patients with DCM is still an open issue. Ventricular
repolarization analysisshould provide relevant information, but QT
interval and QT dispersion failed in predicting arrhythmic
risk.Methods The following parameters were evaluated in 179
consecutive DCM patients without history of sustained
ventriculartachycardia (VT) and/or ventricular fibrillation (VF) at
enrollment: QRS duration, QT interval corrected forheart rate, and
QT dispersion at electrocardiogram (ECG); left ventricular ejection
fraction (LVEF) and left ventricularend-diastolic diameter at
echocardiogram; and nonsustained ventricular tachycardia (NSVT),
heart rate variability(standard deviation of RR intervals), and
ventricular repolarization dynamicity as measured by means of24-h
ECG monitoring, by calculating the slope of linear regression
analysis of QT end and RR intervals (QTeslope)and the value of mean
QT end corrected for heart rate.Results During a mean follow-up of
39 months, 9 patients died suddenly and 15 experienced VT and/or
VF. At multivariateanalysis, LVEF (p 0.047), NSVT (p 0.022), and
QTe-slope (p 0.034) were significantly associated witharrhythmic
events. Among the patients with a low LVEF, NSVT and/or steeper
QTe-slope identified a subgroup athighest arrhythmic
risk.Conclusions In patients with DCM, QT dynamicity is
independently associated with the occurrence of major arrhythmic
eventsand improves the predictive accuracy of stratifying
arrhythmic risk of these patients. (J Am Coll Cardiol
2007;50:22531) 2007 by the American College of Cardiology
Foundation*QT variability strongly predicts sudden cardiac deathin
asymptomatic subjects with mild or moderate leftventricular
systolic dysfunction: a prospective studyGianfranco Piccirillo1*,
Damiano Magr `1, Sabrina Matera1, Marzia Magnanti1, Alessia
Torrini1,Eleonora Pasquazzi1, Erika Schifano1, Stefania Velitti1,
Vincenzo Marigliano1, Raffaele Quaglione2,and Francesco
Barilla`21Dipartimento di Scienze dellInvecchiamento, I Clinica
Medica, Policlinico Umberto I, Universita` La Sapienza, Viale
delPoliclinico, 00161 Rome, Italy and 2 Dipartimento del Cuore e
Grandi Vasi Attilio Reale, Policlinico Umberto I, Universita`La
Sapienza, Rome, ItalyReceived 8 October 2006; revised 13 October
2006; accepted 19 October 2006; online publish-ahead-of-print 13
November 2006Aims The most widely accepted marker for stratifying
the risk of sudden cardiac death (SCD) in postmyocardial infarction
patients is a depressed left ventricular function. Left ventricular
ejectionfractions (EF) of 35% or less increase the risk of sudden
death but values between 35 and 40% raiseconcern. The underlying
pathophysiological mechanism is sustained ventricular tachycardia
or fibrillation,both associated with increased cardiac
repolarization variability. We assessed whether theindices of QT
variability from a short-term electrocardiographic (ECG) recording
predict sudden death.Methods and results A total of 396 subjects
with chronic heart failure (CHF) due to
post-ischaemiccardiomyopathy, with an EF between 35 and 40% and in
NYHA class I, underwent a 5 min ECG recordingto calculate the
following variables: QT variance (QTv), QT normalized for the
square of the mean QT(QTVN), and QT variability index (QTVI).
Corrected QT (QTc) was calculated from a 12-lead ECGrecording. All
participants were followed for 5 years. A multivariable survival
model indicated that aQTVI greater than or equal to the 80th
percentile indicated a high risk of SCD [hazards ratio (HR)4.6, 95%
confidence interval (CI) 1.513.4, P 0.006] and, though to a lesser
extent, a high risk oftotal mortality (HR 2.4, 95% CI 1.24.9, P
0.017). The model including QTVI as a continuous variableconfirmed
a similar high risk for SCD (HR 2.9, 95% CI 1.36.5, P 0.01) and for
total mortality (HR 2.6,95% CI 1.35.2, P 0.008).Conclusion Although
asymptomatic patients with CHF who have a slightly depressed EF are
at low risk ofsudden death, the category is extraordinarily
numerous. The QTVI could be helpful in stratifying the riskof
sudden death in this otherwise undertreated population.*Infarct
Tissue Heterogeneity by Magnetic ResonanceImaging Identifies
Enhanced Cardiac ArrhythmiaSusceptibility in Patients With Left
Ventricular DysfunctionAndr Schmidt, MD*; Clerio F. Azevedo, MD*;
Alan Cheng, MD; Sandeep N. Gupta, PhD;David A. Bluemke, MD, PhD;
Thomas K. Foo, PhD; Gary Gerstenblith, MD; Robert G. Weiss,
MD;Eduardo Marbn, MD, PhD; Gordon F. Tomaselli, MD; Joo A.C. Lima,
MD; Katherine C. Wu, MDBackgroundThe extent of the peri-infarct
zone by magnetic resonance imaging (MRI) has been related to
all-causemortality in patients with coronary artery disease. This
relationship may result from arrhythmogenesis in the infarctborder.
However, the relationship between tissue heterogeneity in the
infarct periphery and arrhythmic substrate has notbeen
investigated. In the present study, we quantify myocardial infarct
heterogeneity by contrast-enhanced MRI andrelate it to an
electrophysiological marker of arrhythmic substrate in patients
with left ventricular (LV) systolicdysfunction undergoing
prophylactic implantable cardioverter defibrillator
placement.Methods and ResultsBefore implantable cardioverter
defibrillator implantation for primary prevention of sudden
cardiacdeath, 47 patients underwent cine and contrast-enhanced MRI
to measure LV function, volumes, mass, and infarct size.A method
for quantifying the heterogeneous infarct periphery and the denser
infarct core is described. MRI indices wererelated to inducibility
of sustained monomorphic ventricular tachycardia during
electrophysiological or device testing.For the noninducible versus
inducible patients, LV ejection fraction (3010% versus 297%,
P0.79), LVend-diastolic volume (22070 versus 22857 mL, P0.68), and
infarct size by standard contrast-enhanced MRIdefinitions (PNS)
were similar. Quantification of tissue heterogeneity at the infarct
periphery was strongly associatedwith inducibility for monomorphic
ventricular tachycardia (noninducible versus inducible: 139 versus
198 g,P0.015) and was the single significant factor in a stepwise
logistic regression.ConclusionsTissue heterogeneity is present and
quantifiable within human infarcts. More extensive tissue
heterogeneitycorrelates with increased ventricular irritability by
programmed electrical stimulation. These findings support
thehypothesis that anatomic tissue heterogeneity increases
susceptibility to ventricular arrhythmias in patients with
priormyocardial infarction and LV dysfunction. (Circulation.
2007;115:2006-2014.)*Cardiac Sodium Channel Gene Variants and
SuddenCardiac Death in WomenChristine M. Albert, MD, MPH; Edwin G.
Nam, BA; Eric B. Rimm, ScD;Hong Wei Jin, PhD; Roger J. Hajjar, MD;
David J. Hunter, MD, ScD;Calum A. MacRae, MB, ChB, PhD; Patrick T.
Ellinor, MD, PhDBackgroundSeveral cardiac ion channel genes have
been implicated in monogenic traits with a high risk of
suddencardiac death (SCD). Mutations or rare variants in these
genes have been proposed as potential contributors to morecommon
forms of SCD, but this hypothesis has not been assessed
systematically.Methods and ResultsWe directly sequenced the entire
coding region and splice junctions of 5 cardiac ion channel
genes,SCN5A, KCNQ1, KCNH2, KCNE1, and KCNE2, in 113 SCD cases from
2 large prospective cohorts of women(Nurses Health Study) and men
(Health Professional Follow-Up Study). Controls from the same
population were thenscreened for the presence of mutations or rare
variants identified in cases, and sequence variants without prior
functionaldata were expressed in Xenopus oocytes to assess their
biophysical consequences. No mutations or rare variants
wereidentified in any of the 53 subjects who were men. In contrast,
in 6 of 60 women (10%), we identified 5 rare missensevariants in
SCN5A that either had been associated previously with long-QT
syndrome (A572D and G615E), had beenreported to alter sodium
channel function (F2004L), or had not been reported previously in
control populations (A572Fand W1205C). Of the 4 variants without
prior functional data, 3 variants were located in the I-II linker
(A572D, A572F,and G615E), and all resulted in significantly shorter
recovery times from inactivation. When compared with 733
controlsamples from the same population, the overall frequency of
these rare variants in SCN5A was significantly higher inthe SCD
cases (6/60, 10.0%) than in controls (12/733, 1.6%;
P0.001).ConclusionFunctionally significant mutations and rare
variants in SCN5A may contribute to SCD risk among
women.(Circulation. 2008;117:16-23.)**Survival Is Similar After
Standard Treatment and ChestCompression Only in Out-of-Hospital
BystanderCardiopulmonary ResuscitationKatarina Bohm, RN; Mrten
Rosenqvist, MD, PhD; Johan Herlitz, MD, PhD;Jacob Hollenberg, MD;
Leif Svensson, MD, PhDBackgroundWe sought to compare the 1-month
survival rates among patients after out-of-hospital cardiac arrest
whohad been given bystander cardiopulmonary resuscitation (CPR) in
relation to whether they had received standard CPRwith chest
compression plus mouth-to-mouth ventilation or chest compression
only.Methods and ResultsAll patients with out-of-hospital cardiac
arrest who received bystander CPR and who were reportedto the
Swedish Cardiac Arrest Register between 1990 and 2005 were
included. Crew-witnessed cases were excluded.Among 11 275 patients,
73% (n8209) received standard CPR, and 10% (n1145) received chest
compression only.There was no significant difference in 1-month
survival between patients who received standard CPR
(1-monthsurvival7.2%) and those who received chest compression only
(1-month survival6.7%).ConclusionsAmong patients with
out-of-hospital cardiac arrest who received bystander CPR, there
was no significantdifference in 1-month survival between a standard
CPR program with chest compression plus mouth-to-mouthventilation
and a simplified version of CPR with chest compression only.
(Circulation. 2007;116:2908-2912.)Key Words: cardiopulmonary
resuscitation heart arrest survival*Delayed Time to Defibrillation
after In-Hospital Cardiac ArrestPaul S. Chan, M.D., Harlan M.
Krumholz, M.D., Graham Nichol, M.D., M.P.H.,Brahmajee K.
Nallamothu, M.D., M.P.H., and the American Heart
AssociationNational Registry of Cardiopulmonary Resuscitation
Investigators*Abstr actN Engl J Med 2008;358:9-17.Copyright 2008
Massachusetts Medical Society.BackgroundExpert guidelines advocate
defibrillation within 2 minutes after an in-hospital cardiacarrest
caused by ventricular arrhythmia. However, empirical data on the
prevalenceof delayed defibrillation in the United States and its
effect on survival are limited.MethodsWe identified 6789 patients
who had cardiac arrest due to ventricular fibrillation orpulseless
ventricular tachycardia at 369 hospitals participating in the
National Registryof Cardiopulmonary Resuscitation. Using
multivariable logistic regression, weidentified characteristics
associated with delayed defibrillation. We then examinedthe
association between delayed defibrillation (more than 2 minutes)
and survival todischarge after adjusting for differences in patient
and hospital characteristics.ResultsThe overall median time to
defibrillation was 1 minute (interquartile range,
