1. Trials and Errors in
cardiovascular medicine- 2013
RAMACHANDRA

2. TMAO α risk of CVD
Trimethylamine-N-oxide (TMAO), produced through intestinal microbial metabolism of dietary
lecithin, appears to contribute to the development of atherosclerotic plaques through its
interactions with macrophages and foam cells. Plasma TMAO levels have been shown to decline
following the suppression of intestinal microorganisms with oral broad-spectrum antibiotics and
then return to near previous levels following the withdrawal of antibiotics . Among a cohort of
4007 patients who underwent elective coronary angiography and were followed for an average
of three years, increased levels of plasma TMAO were associated with significantly greater risk
of death, myocardial infarction, or stroke. Given the association between TMAO levels and
atherosclerotic events as well as the potential for modification of TMAO levels based on
intestinal microbiota, TMAO levels may be a future target for therapies aimed at lowering the
risk of atherosclerotic events

3. Sexual counselling for patients
with CVD
Sexual activity is an important component of quality of life and thus is of concern for patients
with cardiovascular (CVD) disease. To help clinicians and their CVD patients, the American Heart
Association and the European Society of Cardiology published a comprehensive consensus
document on sexual counselling (SC) for individuals with CVD . The document recommends that
SC include a review of medications and potential effects on sexual function, risks related to
sexual activity, the role of regular exercise in supporting intimacy, use of a comfortable setting to
minimize any stress with sexual activity, use of sexual activities that require less energy
expenditure as a bridge to sexual intercourse, avoidance of anal sex, and the reporting of
warning signs experienced with sexual activity. We support recommendations made in this
document.

4. DPP-4 inhibitors and
cardiovascular safety
In two different trials, patients with type 2 diabetes and either a history of cardiovascular
disease or multiple risk factors for vascular disease were randomly assigned to one of the DPP-4
inhibitors (saxagliptin, alogliptin) or placebo, in addition to other diabetes medications
(predominantly metformin, sulfonylureas, insulin) . The primary endpoint (a composite endpoint
of cardiovascular death, nonfatal myocardial infarction, or nonfatal ischemic stroke) occurred in
a similar proportion of patients in both groups. Although heart failure was infrequent in both
groups, significantly more patients in the saxagliptin group were hospitalized for heart failure.
Although these data are reassuring in that there does not appear to be an increased risk of
adverse cardiovascular outcomes with short-term (two-year) treatment with DPP-4 inhibitors
used in combination with other agents, longer-term clinical trials are needed to definitively
assess the cardiovascular safety of DPP-4 inhibitors.

5. Beta blockade in septic shock
Beta blockade may have potential benefit in limiting harmful effects associated with the
adrenergic surge that occurs in patients with sepsis. An open-label, single center trial
randomized 154 patients with septic shock to an infusion of esmolol (short-acting beta blocker)
or standard therapy. All patients on esmolol achieved the pre-set target heart rate of 80 to 94
beats/min without a significant drop in mean arterial pressure. Compared to patients on
standard therapy, patients receiving esmolol had improvements in left ventricular stroke work
index, markers of end-organ function (eg, glomerular filtration rate), and a reduced need for
vasopressors that were associated with a mortality benefit at 28 days. Further validation of
these findings is warranted before esmolol can be routinely recommended as a therapy in
patients with septic shock.

6. TLT for PVT during pregnancy
Experience with the management of prosthetic valve thrombosis in pregnant women is limited,
with no randomized trials and most data from published case series. In the largest reported
series of thrombolysis as the initial therapy for prosthetic valve thrombosis during pregnancy, all
patients (24 patients, 28 thrombolytic episodes) had successful thrombolysis, with no maternal
mortality and five fetal deaths (20 percent). Given the small numbers and concerns regarding
fetal mortality, we continue to suggest surgery rather than thrombolytic therapy for thrombosis
of left-sided valves, and thrombolytic therapy for right-sided valves.

7. Dabigatran not indicated with
mechanical heart valves
Dabigatran is an oral direct thrombin inhibitor used as an anticoagulant for atrial fibrillation and
venous thromboembolism treatment and prophylaxis. In the RE-ALIGN trial, patients who had
undergone mechanical heart valve replacement were randomly assigned to receive dabigatran
or warfarin postoperatively. The trial was stopped early because of an excess of thromboembolic
and bleeding events in the dabigatran group. We recommend not using dabigatran in patients
with mechanical heart valves. Warfarin or another vitamin K antagonist is the preferred
anticoagulant in such patients.

8. Early surgery for flail mitral valve
leaflet
A study from an international registry of patients with flail mitral valve leaflets found that early
MV surgery was associated with higher long-term survival rates and lower rates of heart failure
than initial medical management .

9. Mitral valve surgery for ischemic
mitral regurgitation
Limited data have been available to guide surgical treatment for severe ischemic mitral
regurgitation (MR). A randomized trial comparing mitral valve repair and chordal-sparing mitral
valve replacement found no significant difference at one year in left ventricular reverse
remodeling or survival. However, the rate of recurrent moderate or severe MR was higher in
patients undergoing mitral valve repair.

10. Premature cessation of dual
antiplatelet therapy after PTCA
The strongest predictor of stent thrombosis within the first year after percutaneous coronary
intervention (PCI) is the premature cessation of dual antiplatelet therapy (DAPT). The
relationship between cessation of DAPT and adverse cardiac events, including stent thrombosis,
was studied prospectively using data from the large PARIS registry . Although most adverse
events following PCI occurred in patients who were still receiving DAPT, early DAPT cessation
increased the risk. The causes of cessation included physician recommendation
(discontinuation), an event such as upcoming surgery (interruption), or bleeding/noncompliance
(disruption). The risk of an adverse event was highest in patients who stopped DAPT due to
disruption.

11. Clopidogrel failure in patients on
PPI
In ex vivo experiments on human cells and tissue as well as in an in vivo mouse model, proton
pump inhibitors (PPIs) have been shown to inhibit the enzymatic degradation of asymmetrical
dimethylarginine (ADMA) and therefore may increase levels of ADMA . Cohort studies have
shown an association between elevated levels of serum ADMA and an increased risk of acute
coronary events. While these findings suggest a potential mechanism for the increased number
of cardiac events following coronary artery intervention among patients taking a PPI in addition
to clopidogrel, this risk may also apply to the general population of PPI users. However, there are
currently no published clinical data to support or refute this association, and at present
these laboratory findings should not change the clinical management of patients.

12. DAPT after DES
● DES LATE : 5054 low-risk patients who were treated with aspirin and clopidogrel following
DES and were free of major adverse cardiovascular events and major bleeding for at least 12
months to receive aspirin alone or to continue clopidogrel plus aspirin. At 24 months, there was
no difference between the groups in the risk of the primary composite end point (death from
cardiac causes, myocardial infarction, or stroke) or major bleeding.
●OPTIMIZE :Stable coronary artery disease or history of low-risk acute coronary syndrome who
underwent DES placement were randomly assigned to clopidogrel for 3 or 12 months and aspirin
indefinitely. There was no difference in the rate of the primary composite end point including allcause death, MI, stroke, or major bleeding. The rate of major bleeding was no significantly lower
with the shorter duration of clopidogrel. This trial and others raise the possibility that, for some
patients who have received DES, dual antiplatelet therapy for less than one year may be a
reasonable strategy.
Openion:Must for one year

13. Cardiovascular risk of NSAIDs
The magnitude of risk is best illustrated by a meta-analysis of data from over 300,000
participants in over 700 trials that compared nonselective NSAIDs (used at the upper end of
their dose range) or coxibs with either placebo or another nonselective NSAID or coxib
. Compared with placebo, use of high-dose diclofenac or a coxib increased major cardiovascular
events (nonfatal MI, nonfatal stroke, or vascular death) by about 40 percent. High-dose
ibuprofen increased the risk of major coronary events but not major vascular events. High-dose
naproxen did not increase major cardiovascular events, major coronary events, or vascular
death. The estimated excess absolute risk of a major vascular event or death with use of
diclofenac, coxib, and possibly ibuprofen was two events per 1000 persons per year in patients
at low baseline cardiovascular risk and seven to eight events per 1000 persons per year,
including two fatal events, in patients at high baseline cardiovascular risk. Naproxen is therefore
the preferred nonselective NSAID when long-term use is needed in patients at increased risk for
cardiovascular disease.

14. "Smoker's paradox"
Some studies of clopidogrel therapy in patients with coronary artery disease have
found decreased clinical benefit for non-smokers compared to smokers. This has been termed
a "smoker's paradox." The magnitude of the effect of smoking on the efficacy of clopidogrel was
evaluated in a meta-analysis of randomized trials, involving nearly 75,000 patients, in which
clopidogrel was compared to placebo, aspirin, or another platelet P2Y12 receptor
blocker . Compared to control therapy, a 25 percent reduction in the primary composite
outcome (cardiovascular death, myocardial infarction, and stroke) was seen in smokers assigned
to clopidogrel, whereas non-smokers had an 8 percent reduction

15. Evolocumab for drug-resistant
hypercholesterolemia
Therapy of drug-resistant hypercholesterolemia is limited by a paucity of effective, safe, and
convenient interventions. One such emerging therapy is evolocumab (AMG 145), a monoclonal
antibody to PCSK9. Phase II studies of 12 week duration have shown the drug to be effective and
safe. Longer-term efficacy and safety was evaluated in the OSLER trial, which randomly assigned
patients to receive either open-label, subcutaneous evolocumab every four weeks with standard
of care (SOC) or SOC alone . After one year, treatment with evolocumab lowered low-density
lipoprotein cholesterol by about 52 percent, while no severe or life-threatening adverse events
were attributed to the drug.

16. ACC/AHA CVD risk-2013
The American College of Cardiology/American Heart Association (ACC/AHA) guidelines state
that it is “reasonable” to assess risk factors in most adults every four to six years. For patients
without known cardiovascular disease (CVD), the guidelines make recommendations for
moderate- or high-intensity statin therapy primarily based on calculated CV risk and presence or
absence of diabetes. For most patients with known CVD, the guidelines recommend treatment
with high-intensity statin therapy. Unlike ATP III, these ACC/AHA guidelines focus more on
intensity of statin therapy, and less on LDL-cholesterol goals and use of non statin lipid lowering
agents.

17. siRNA for amyloidosis
Novel approaches to the treatment of amyloidosis are under investigation, including the use of
RNA interference to inhibit the production of amyloidogenic precursors, such as transthyretin.
Mutant transthyretin can cause familial amyloidotic neuropathy, while deposition of wild-type
(non-mutant) transthyretin, termed senile amyloid, can result in a restrictive cardiomyopathy
and carpal tunnel syndrome. In phase I proof-of-principle trials, the intravenous administration
of anti-transthyretin small interfering ribonucleic acid (siRNA) formulations in lipid nanoparticles
significantly reduced the production of both mutant and non-mutant transthyretin in patients
with transthyretin amyloidosis and in healthy volunteers . Further study will be required to
determine the effectiveness and safety of this approach for the treatment of transthyretinrelated forms of amyloidosis.

18. Colchicine for Rx of a first
episode of acute pericarditis
Randomized trials have shown the effectiveness of colchicine in the treatment of recurrent
pericarditis, but evidence has been limited for its use in treatment of a first episode of acute
pericarditis. In the ICAP trial, in patients with a first episode of acute pericarditis, adding
colchicine to standard antiinflammatory therapy reduced the risk of recurrence compared with
antiinflammatory therapy alone . It is recommend that patients with a first episode of acute
pericarditis be treated with colchicine in addition to standard antiinflammatory therapy.

19. Asymptomatic LV dysfunction &
BNP
The STOP-HF trial randomly assigned 1374 patients at increased risk for heart failure (HF) (eg,
hypertension, hypercholesterolemia, obesity, moderate to severe valvular heart disease,
arrhythmia, diabetes, or vascular disease) to usual care or screening with BNP and further
assessment and care if the BNP was elevated . LV dysfunction, heart failure, and rates of
emergency hospitalization for major cardiovascular events (including heart failure) occurred less
often in the intervention group. Confirmatory studies are awaited before screening with BNP is
recommended for high-risk populations.

20. Macitentan for PAH
Endothelin receptor antagonists (ERAs) are known to improve exercise capacity and slow disease
progression in patients with idiopathic pulmonary arterial hypertension (PAH). However, the
impact of ERAs on mortality is unproven. Macitentan is an oral ERA that was studied in a
randomized placebo-controlled trial of 250 patients with PAH . Compared to placebo, two-year
treatment with macitentan (with or without other treatments) resulted in fewer deaths and
slower disease progression as a combined outcome. Although the study was not powered to
examine mortality as an independent outcome, macitentan had a greater impact on delaying
disease progression than on mortality. Macitentan was generally well-tolerated with
nasopharyngitis and anemia as its major side effects. This drug is not yet commercially available
for use.

21. CRT in patients with narrow QRS
Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in selected patients
with chronic systolic heart failure and wide QRS. Some patients with narrow QRS also have
mechanical dyssynchrony but risks and benefits of CRT in this population are uncertain. In the
EchoCRT trial, patients with New York Heart Association functional class III or IV heart failure, LV
ejection fraction ≤35 percent, QRS duration <130 ms, and mechanical dyssynchrony underwent
implantation of a combined CRT and implantable cardioverter-defibrillator (ICD) device (CRT-D)
and were then randomly assigned to be programmed to CRT or no CRT . The study was stopped
for futility and showed no benefit from CRT for the primary outcome (a composite of death
from any cause or first hospitalization for worsening heart failure). Deaths occurred more
frequently in the CRT group.

22. Rx of anaemia in heart failure
A restrictive transfusion policy for most patients, and we recommend against use of
erythropoiesis stimulating agents based upon the results of a systematic review of six
randomized trials and 26 observational studies . The review found low-strength evidence
showing no benefit from liberal transfusion protocols compared with more restrictive
protocols. The review also found moderate- to high-strength evidence that erythropoiesis
stimulating agents do not provide consistent benefit in patients with mild to moderate anemia
but are associated with an increased risk of venous thromboembolism.

23. Rivaroxaban + aspirin/clopidogrel
for ACS
Favorable findings for the use of rivaroxaban in patients with acute coronary syndromes (ACS) in
the ATLAS 2 ACS-TIMI 51 trial. The European Medicines Agency approved this dose in March of
2013 for secondary prevention after stabilized ACS in patients who had positive biomarkers for
cardiac damage at the index event. Rivaroxaban 2.5 mg may be used in such patients who are
not at high bleeding risk. The duration of treatment with rivaroxaban is approximately one year,
as studied in the randomized trial. Patients may reasonably choose to not take rivaroxaban if
they are particularly concerned about the bleeding risk. This recommendation does not apply to
patients taking either prasugrel or ticagrelor.

24. Bypassing the ED
Time to onset of reperfusion is a critical determinant of outcome with primary percutaneous
coronary intervention (PPCI) in patients with ST-elevation myocardial infarction (STEMI). In an
observational study of 12,158 STEMI patients diagnosed with a prehospital electrocardiogram,
10.5 percent bypassed the ED and were taken directly to the cardiac catheterization
laboratory . ED bypass shortened the time from first medical contact to PPCI and there was a
trend toward a lower adjusted mortality. We support the use of this approach when feasible.

25. DBT α mortality?
Shorter door-to-balloon (D2B) times have been associated with improved survival in patients
with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary
intervention. In a large registry study (2005 to 2009), median D2B time fell from 83 to 67
minutes, comparing the first to the last 12 months of the study . Despite this significant
improvement, there was no change in risk-adjusted in-hospital mortality. This unexpected
finding may indicate that with shorter D2B times, other factors, such as the total duration of
ischemia, may become more important in determining outcome.

26. Timing of P2Y12 receptor blocker in
NSTEACS
Platelet P2Y12 receptor blocker (either ticagrelor or clopidogrel) be given at the time of diagnosis
rather than after diagnostic angiography. A third P2Y12 receptor blocker, prasugrel, was found to
be superior to clopidogrel when given following angiography in the TRITON-TIMI 38 trial. In the
ACCOAST trial, 4000 patients with NSTEACS were randomly assigned to receive prasugrel either
before or after angiography . The rate of the primary composite efficacy end point was similar in
the two groups, but the rate of major bleeding was greater in the preprocedure treatment
group. Therefore, NO f prasugrel prior to angiography, both because of an increased bleeding
risk and because it was not evaluated for preprocedure use in the TRITON-TIMI 38 trial

27. PCI of non-culprit vessel in STEMI
PRAMI trial raises the possibility that "preventive" PCI of non-culprit vessels may improve
clinical outcomes . PRAMI, which intended to randomly assign 600 patients with acute STEMI to
either preventive PCI or no preventive PCI after successful primary PCI, was terminated after
enrollment of 465 individuals. The incidence of the primary composite outcome (cardiac death,
nonfatal MI, or refractory angina) was significantly lower (9 versus 23 percent) with non-culprit
PCI. These findings are subject to trial limitations, including a composite end point with a small
number of events and the fact that the trial was stopped early. Until further data are available,
please wait.

28. Anticoagulants in STEMI
The HORIZONS AMI trial, published about five years ago, found that for patients with STelevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention
(PCI), outcomes were better with anticoagulant therapy using bivalirudin compared to a heparin.
In the EUROMAX trial, 2218 such patients were randomly assigned to prehospital
administration of bivalirudin or a heparin . The findings in EUROMAX were similar to those in
HORIZONS AMI: bivalirudin was associated with a higher rate of stent thrombosis but a lower
rate of major bleeding, with an overall trend toward lower mortality. This recent trial supports
our prior preference for bivalirudin (with provisional GP IIb/IIIa inhibitor) to heparin (with
a glycoprotein IIb/IIIa inhibitor) for most patients with STEMI undergoing primary PCI.

29. Aspiration thrombectomy
One strategy to improve reperfusion is to perform thrombectomy prior to stenting. A metaanalysis and subsequent randomized trial of patients who received thrombus aspiration
(manual) at the time of PCI found better outcomes with aspiration compared with no
aspiration; mechanical thrombectomy, however, did not improve outcomes. Based on the
available evidence, we suggest that many patients with STEMI undergoing PCI receive aspiration
thrombectomy

30. Remote IPC in CABG
Remote ischemic preconditioning of the left arm was compared with no RIPC in a randomized
trial of 329 individuals scheduled to undergo elective coronary artery bypass graft surgery
(CABG) . The extent of perioperative myocardial injury, as reflected by measurement of cardiac
troponin I (the primary end point), was significantly less in the RIPC group. All-cause mortality, a
secondary end point, was also lower in the RIPC group at approximately one year. Further
confirmatory studies are needed prior to our recommending such therapy

31. Antioxidant/vitamins to prevent
postoperative AFib
This trial found that patients who received vitamins C and E, in addition to n-3 polyunsaturated
fatty acids, had a lower rate of postoperative AF than those who received placebo,
although there were a small number of events

32. Bleeding with Dabigatran
In a registry study, which compared 8936 patients taking warfarin to 4987 taking dabigatran,
rates of major bleeding were comparable and the risk of intracranial hemorrhage was lower in
the dabigatran group at dabigatran doses of 110 or 150 mg twice daily . Based on all available
evidence, we believe the risk of major bleeding is comparable between dabigatran 150 mg and
warfarin and is less with dabigatran 110 mg compared to warfarin. Selection of the dose of
dabigatran should take into account efficacy as well as bleeding risk.

33. Switching from warfarin to
rivaroxaban in patients with AF
The optimal method of switching patients with atrial fibrillation (AF) from warfarin to a newer
oral anticoagulant, such as rivaroxaban, is not known. The protocol for the ROCKET AF trial,
which compared warfarin to rivaroxaban, mandated that patients who were previously taking
warfarin could transition to rivaroxaban only when the International Normalized Ratio (INR) was
<3.0. Rivaroxaban use in this subgroup of patients resulted in similar efficacy and safety
(primary) outcomes as in the entire cohort of patients assigned to rivaroxaban. Based on these
results, we suggest starting rivaroxaban (and stopping warfarin) in AF patients previously treated
with warfarin when the INR is <3.0.

34. Percutaneous plugging of LAA
The majority of thrombi that occur in patients with nonvalvular atrial fibrillation (AF) are located
within or involve the left atrial appendage (LAA). The importance of the LAA in thromboembolic
risk provides the rationale for ligation, amputation, or occlusion of the LAA in AF patients who
are candidates for but cannot receive oral anticoagulation. Three recent, small studies of
percutaneous procedures designed to exclude the LAA (the LARIAT system, thoracoscopic
appendectomy, and the Amplatzer Cardiac Plug) have confirmed safety and efficacy found in
earlier studies . For nonvalvular AF patients who are at high stroke risk but who are not
candidates for long-term oral anticoagulation, may be benefitted by one of these procedures

35. ICD without lead
The standard implantable cardioverter-defibrillator (ICD) with transvenous leads is associated
with a risk of vascular complications and systemic infection (ie, endocarditis). An entirely
subcutaneous ICD system has been developed to minimize this risk. In a prospective,
nonrandomized, multicenter trial of the subcutaneous ICD in patients with a standard indication
for an ICD but no pacing requirement, primary end points for both safety and efficacy were
achieved. While these results are encouraging, long-term safety and efficacy data are required
prior to routine implantation of the subcutaneous ICD

36. Cognitive impairment after RFA
The prevalence of cognitive impairment after radiofrequency catheter ablation (RFA) was
evaluated in a study of 150 patients with atrial arrhythmias . After 90 days following the
procedure, neurocognitive dysfunction was found in 13, 20, 3, and 0 percent of patients with
paroxysmal atrial fibrillation (AF), persistent AF, supraventricular tachycardia, and matched AF
patients awaiting RFA (the control group), respectively. However, another study of 37 patients
with paroxysmal AF detected no decline in neurocognitive function at six months,
including 16 patients in whom cerebral lesions were seen on magnetic resonance imaging
performed 48 hours post-RFA

37. Antithrombotic regimens Vs.
Antiplatelet
An observational study in over 12,000 patients with atrial fibrillation who were undergoing
percutaneous coronary intervention or who had a recent myocardial infarction (MI) compared
outcomes for three antithrombotic regimens: aspirin, clopidogrel, and OAC (triple therapy); OAC
plus clopidogrel; or OAC plus aspirin . Compared to triple therapy, there was a trend at one year
toward a lower risk of MI or coronary death for OAC plus clopidogrel, while the risk was slightly
higher for OAC plus aspirin. As expected, bleeding risk was higher with triple therapy.

38. β blockers reduce inappropriate
Shocks
The choice of beta blocker may have an impact on reducing inappropriate therapies (both antitachycardia pacing and shocks) in patients with an implantable cardioverter-defibrillator (ICD). In
a post-hoc analysis of beta blocker usage in the MADIT-CRT study, in which 14 percent of
patients experienced inappropriate ICD therapies during 3.4 years of follow up, patients
receiving carvedilol had significantly fewer inappropriate ICD therapies compared to those
receiving metoprolol . While these data are promising, the results should be considered
hypothesis-generating given the retrospective nature of the study, the non-randomized
distribution of beta blockers, and that this was not a pre-specified outcome for the study

39. Edoxaban to Rx AF
The newer oral anticoagulants dabigatran, apixaban, and rivaroxaban are preferred to warfarin
in many patients with atrial fibrillation (AF). The ENGAGE AF-TIMI 48 trial randomly assigned
moderate- to high-risk AF patients (mean CHADS score 2.8) to one of two doses of edoxaban, a
newer oral factor Xa inhibitor, or to adjusted dose warfarin . The risk of stroke or systemic
embolization was comparable in the three groups, while the risk of major bleeding was
significantly lower with either dose of edoxaban compared to warfarin. Edoxaban is not available
in Europe or the United States and is available in Japan for the prevention and treatment of
venous thromboembolism

40. Genotyping ineffective for
improving warfarin initial dosing
Initial dosing of vitamin K antagonists (eg, warfarin) is uncertain; pharmacokinetics can be
affected by polymorphisms in genes that control drug or clotting factor metabolism. Three
trials evaluated the role of genotyping in determining the initial drug dose by randomizing
patients to clinically-based dosing or dosing based on genotype . The time in the
therapeutic INR range, a surrogate for efficacy and adverse events, was unaffected by genotypebased dosing in two trials and minimally improved in the third. Overall bleeding rates were
similar between arms in all three trials. Genetic polymorphism dose not guide vitamin K
antagonist initial dosing in routine clinical practice

41. JNC-8

42. From: 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the
Panel Members Appointed to the Eighth Joint National Committee (JNC 8)
JAMA. 2013;():. doi:10.1001/jama.2013.284427
Figure Legend:
Comparison of Current Recommendations With JNC 7 Guidelines
Date of download: 1/5/2014
Copyright © 2012 American Medical
Association. All rights reserved.

43. ACC/AHA CV risk score
calculator-2013
http://cardiosource.org/~/media/Files/Science%20and%20Quality/Guidelines/Omnibus%20Spre
adsheet%20NEW.aspx?w_nav=LN

44. Canadian cardiovascular society HF
Guideline 2013 for children
The NYHA/Ross classification is a suitable basis for symptom stratification of patients with
established chronic HF, but is not essential to establishing the diagnosis, or determining the
prognosis of HF in children (Strong Recommendation, Moderate-Quality Evidence).