EAL

HF: CoEnzyme Q10 (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To investigate if the administration of CoQ in conjunction with standard medical therapies has been reported to augment myocardial kinetics, increase cardiac output, elevate the ischemic threshold and enhance functional capacity in patients.

Inclusion Criteria:

Inclusion criteria included Left ventricular ejection fraction (LVEF) of less than 45% determined by contrast or radionuclide angiocardiography and left ventricular dilatatic as well as documented physical signs (pulmonary rates and/or third heart sound) or radiographic evidence of left heart dysfunction (cardiothoracic ratio > 0.50 or a transverse heart diameter exceeding the normal value for the patient's height and weight by >10% with associated pulmonary vascular congestion) at some time in the past.

Exclusion Criteria:

Exclusion criteria included significant valvular or congenital heart disease, inability or unwillingness to cooperate with the protocol, history or an acute myocardial infarction within the past 3 months, active myocarditis, uncontrolled hypertension or diabetes mellitus, unstable angina or chest pain requiring more than 5 nitroglycerins per week, atrial fibrillation with rapid (>110) ventricular response despite drug therapy or sustained ventricular tachycardia refractory to medical or surgical interventions, or taking oral hypoglycemics or HMG-CoA reductase inhibitors.

Description of Study Protocol:

Recruitment

Patients were selected consecutively from the office practice and were comparable to any presenting to a tertiary care center for treatment of congestive cardiomyopathy.

Design

This was a before-after study described in the paper as an open-label, single-limb treatment format.

Blinding used (if applicable)

The nuclear technician was blinded to study participant identity.

Intervention (if applicable)

All patients received 30 mg CoQ three times a day for 16 weeks.

Statistical Analysis

Data are expressed as percents or as mean ± SEM. Comparison of baseline and treatment exercise values utilized the student t-test for paired data. Correlation analysis used standard linear regression. Significance of data was determined at the level of p < 0.05 (two-tailed).

Data Collection Summary:

Timing of Measurements

The measurements (rest and stress first-pass radionuclide angiography (FPRNA)) and a physical examination were performed on all patients at baseline and after four months. The resting FPRNA was also performed at the 2 month interval.

Dependent Variables

Variable 1: Resting hemodynamics were determined by physical examination and by FPRNA. B-blockers were stopped 24 hours prior to the testing. A short 20-gauge Teflon intravenous catheter was inserted in an antecubital vein. Electrocardiogram leads were placed on the chest and sphygmometer cuff was put on the arm not used for injection. Patients were seated in erect position on a bicycle ergometer (Fintron: Lumex, Inc) and resting blood pressure and an electrocardiogram were obtained. Acquisition of the resting study involved a bolus injection of technetium-99m diethylenetriamine penta-acted acid with counts recorded at 25-millisecond intervals for a 30-second period.

Variable 2: Exercise hemodynamics were performed after the resting protocol described above was completed. The exercise was initiated at 200 kpm/min and increased by like increments every 2 minutes. The electrocardiogram was monitored continuously with hard copies recorded at 2-minute intervals during exercise and into recovery. Exercise continued until achievement of at least 85% age-predicted maximal heart rate, exercise for at least five minutes, development of chest pain suggestive of ischemia, identification of ischemic ST changes, or until extreme fatigue or shortness of breath intervened. At commencement of these points, a 25-mCi bolus was delivered and exercise continued until the completion of data acquisition. Data acquisition utilized a multicrystal gamma camera equipped with a 1-inch parallel-hole collimator. A curve representing count changes within the left ventricle was employed to identify the times of end-systole and end-diastole of individual beats. Data collected for 3-6 consecutive beats starting at end-diastole produced an average or representative cardiac cycle. The LVEF was calculated from the back-ground-corrected representative cycle as end-diastolic counts minus end-systolic counts divided by end-diastolic counts. The area of the end-diastolic image was obtained by planimetry and its length was measured with a sonic digitizing device linked to a PDP-1145 computer. The LVEDV was calculated according to the arm-length method of Dodge with derivation of all other hemodynamic variables for the LVEF by accepted relationships. Estimation of MVO₂ was done by two methods: the rate-pressure product and the formula, heart rate x brachial systolic blood pressure (SBP). Evaluation of myocardial contractility used a modification of SBP/ESVI. Systemic vascular resistance was estimated as the mean blood pressure divided by the cardiac output times 80. Approximation of ventricular compliance utilized the percent change (rest to stress) in the stroke volume divided by the end-diastolic volume. Assessment of reliance upon the Frank-Starling mechanism to augment the LVEF employed calculation of stroke work divided by EDV.

Independent Variables

COQ

Control Variables

Heart rate, systolic blood pressure, mean blood pressure, LVEF, cardiac output, cardiac index, stroke volume index, end-diastolic area, SBP/ESVI, stroke work/EDV, MV_o2, and SVR at rest.Heart rate, systolic blood pressure, mean blood pressure, LVEF, cardiac output, cardiac index, stroke volume index, end-diastolic area, SBP/ESVI, stroke work/EDV, MV_o2, SVR double product, workload, exercise duration,%maximum predicted heart rate, and %deltaSV/EDV during rest.

Description of Actual Data Sample:

Initial N: 17 (12 males and 5 females)

Attrition (final N):

15 completed the study. All 17 completed the 2-month interval study. One patient died suddenly and the other was hospitalized with severe chest pain and underwent triple-vessel bypass surgery.

Age:

46-80 years

Ethnicity:

Caucasian

Other relevant demographics:

All patients had a NYHA mean functional class of 3.0 ± 0.4.

Anthropometrics (e.g., were groups same or different on important measures)

All patients were the same on important measurements.

Location:

United States physician's office practice

Summary of Results:

Variables

Treatment Group

Measures and confidence intervals

Control group

Measures and confidence intervals

Statistical Significance of Group Difference

Dep var 1

Resting Hemodynamics:

Heart rate (bpm)

Systolic blood pressure (mm Hg)

Mean blood pressure(mm Hg)

LVEF (%)

Cardiac output (L/min)

Cardiac index (L/min/m²)

Stroke volume indes (mL/beat/m²)

End-diastolic area (cm²)

SBP/ESVI (mm Hg-mL^-1)

Stroke work/EDV (mL-mm Hg)

MV_o2 (mL-min^-1-100 g)

SVR (dyn-s-cm^-5)

Mean, CI.

72.6 ± 8.4

145.2 ± 15.2

100.8 ± 8.6

23.4 ± 6.8

5.1 ± 0.6

3.0 ± 0.6

36.0 ± 6.1

55.7 ± 4.2

1.45 ± 0.1

0.29 ± 0.3

31.9 ± 2.8

1568.2 ± 126

Mean, CI.

76.6 ± 9.9

138.8 ± 16.5

96.6 ± 6.2

31.5 ± 6.0

5.9 ± 0.8

3.8 ± 0.8

42.8 ± 6.2

51.0 ± 4.4

1.62 ± 0.2

0.31 ± 0.5

30.2 ± 2.4

1387.2 ± 108

Stat signif difference between groups

< 0.01

<0.01

<0.025

<0.01

<0.001

Dep var 2

Exercise Hemodymamics:

Heart rate (bpm)

Systolic blood pressure (mm Hg)

Mean blood pressure(mm Hg)

LVEF (%)

Cardiac output (L/min)

Cardiac index (L/min/m²)

Stroke volume indes (mL/beat/m²)

End-diastolic area (cm²)

SBP/ESVI (mm Hg-mL^-1)

Stroke work/EDV (mL-mm Hg)

MV_o2 (mL-min^-1-100 g)

SVR (dyn-s-cm^-5)

Double product (10^-3)

Workload (kpm)

Exercise duration (s)

%Maximum predicted heart rate

%deltaSV/EDV

132.2 ± 12.6

174.3 ± 10.8

128.5 ± 8.2

27.2 ± 6.8

9.4 ± 1.2

4.8 ± 0.8

43.2 ± 6.2

54.6 ± 4.7

1.67 ± 0.1

0.34 ± 0.6

54.2 ± 3.4

1166.5 ± 102

23.6 ± 2.4

387.2 ± 54.4

290.6 ± 66.2

76.4 ± 9.2

-2.9 ± 10.3

138.8 ± 11.4

166.0 ± 9.3

118.2 ± 7.8

33.9 ± 5.5

11.2 ± 2.2

5.4 ± 0.8

48.9 ± 6.9

51.3 ± 4.0

1.98 ± 0.3

0.35 ± 0.8

50.4 ± 4.6

958.7 ± 138

21.8 ± 2.2

442.5 ± 48.8

364.4 ± 58.2

78.3 ± 8.2

+7.6 ± 9.8

<0.05

<0.01

<0.005

<0.05

<0.025

<0.01

<0.025

<0.001

<0.05

<0.01

<0.001

<0.01

etc

Other Findings

Functional class improved 20% (3.0 ± 0.4 to 2.4 ± 0.6, p<0.001) and there was a 27% improvement in mean CHF scores (2.8 ± 0.4 to 2.2 ± 0.4, p<0.001).

The following percent changes in resting variables were:

LVEF +34.8

cardiac output +15.7

stroke volume index +18.9

EDV area - 8.4

SBP -4.4

E_max(SBP + ESVI) +11.7

Therapy was associated with a mean 25.4 % increase in exercise duration and a 14.3% increase in workload.

The following percent changes in exercise variables were:

LVEF +24.6

cardiac output +19.1

stroke volume index +13.2

heart rate +6.5

SBP -4.3

SBP/ESVI +18.6

EDV area -6.0

MV_o2 -7.0

ventricular compliance (%delta SV/SDV) +>100

Side effects were reported by one patient who experienced dyspepsia which resolved when the CoQ10 was taken with meals.

Author Conclusion:

COQ is associated with significant functional, clinical, and hemodynamic improvements within the context of an extremely favorable benefit-to-risk ratio. COQ enhances cardiac output by exerting mild vasodilatation as well as a positive inotropic effect upon the myocardium. This is achieved without increasing myocardial oxygen consumption requirements or wall stress (EDV).

Funding Source:

University/Hospital:

Massapequa General Hospital, Finch University of Health Sciences, Chicago Medical School

Reviewer Comments:

This was a very small study which objectively studied the resting and hemodynamic effects of COQ.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	N/A
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	Yes
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	N/A
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	Yes
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	N/A
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	N/A
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	N/A
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		No
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	No
10.	Is bias due to study's funding or sponsorship unlikely?		???
	10.1.	Were sources of funding and investigators' affiliations described?	No
	10.2.	Was the study free from apparent conflict of interest?	Yes