Multivessel FFR and Prognosis

Lee et at (European Heart Journal (2017) 00, 1–8 CLINICAL RESEARCH
doi:10.1093/eurheartj/ehx458)  report on the relationship between total atherosclerotic physiological burden as assessed by multivessel FFR and 2 year cardiac event rates.

ABSTRACT

Aims

There are limited data on the clinical implications of total physiologic atherosclerotic burden assessed by invasive
physiologic studies in patients with coronary artery disease. We investigated the prognostic implications of total physiologic atherosclerotic burden assessed by total sum of fractional flow reserve (FFR) in three vessels (3V-FFR).

Methods and results

A total of 1136 patients underwent FFR measurement in three vessels (3V FFR-FRIENDS study, NCT01621438). The patients were classified into high and low 3V-FFR groups according to the median value of 3V-FFR (2.72). Theprimary endpoint was major adverse cardiac events (MACE, a composite of cardiac death, myocardial infarction and ischaemia-driven revascularization) at 2 years. Mean angiographic percent diameter stenosis and FFR were 43.7 ± 19.3% and 0.90 ± 0.08, respectively. There was a negative correlation between 3V-FFR and estimated 2-year MACE rate (P < 0.001). The patients in low 3V-FFR group showed a higher risk of 2-year MACE than those in the high 3V-FFR group [(7.1% vs. 3.8%, hazard ratio (HR) 2.205, 95% confidence interval (CI) 1.201–4.048, P = 0.011]. The higher 2-year MACE rate was mainly driven by the higher rate of ischaemia-driven revascularization in the low 3V-FFR group (6.2% vs. 2.7%, HR 2.568, 95% CI 1.283–5.140, P = 0.008). In a multivariable adjusted model, low 3VFFR was an independent predictor of MACE (HR 2.031, 95% CI 1.078–3.830, P = 0.029).

Conclusion

Patients with high total physiologic atherosclerotic burden assessed by 3V-FFR showed higher risk of 2-year clinical events than those with low total physiologic atherosclerotic burden. The difference was mainly driven by
ischaemia-driven revascularization for both functionally significant and insignificant lesions at baseline. Three-vessel FFR might be used as a prognostic indicator in patients with coronary artery disease.

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Acute Stress-induced Cardiomyopathy

Dawson presents a useful review of Takotsubo cardiomyopathy: (http:// dx. doi. org/ 10. 1136/heartjnl- 2017- 311579).
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Prognosis of Unexplained Syncope and Orthostatic Hypotension

Yasa et al (Yasa E, Ricci F, Magnusson M, et al. Heart Published Online
First: doi:10.1136/heartjnl-2017-31185) report a prospective population study to assess the outcome of patients with discharge diagnoses of unexplained syncope or orthostatic hypotension.

Abstract

Objective

To investigate the relationship of hospital
admissions due to unexplained syncope and orthostatic
hypotension (OH) with subsequent cardiovascular events
and mortality.

Methods

We analysed a population-based prospective
cohort of 30 528 middle-aged individuals (age 58±8
years; males, 40%). Adjusted Cox regression models
were applied to assess the impact of unexplained
syncope/OH hospitalisations on cardiovascular events
and mortality, excluding subjects with prevalent
cardiovascular disease.

Results

After a median follow-up of 15±4 years, 524
(1.7%) and 504 (1.7%) participants were hospitalised
for syncope or OH, respectively, yielding 1.2 hospital
admissions per 1000 person-years for each diagnosis.
Syncope hospitalisations increased with age (HR, per
1 year: 1.07, 95% CI 1.05 to 1.09), higher systolic
blood pressure (HR, per 10 mm Hg: 1.06, 95% CI 1.01
to 1.12), antihypertensive treatment (HR: 1.26, 95% CI
1.00 to 1.59), use of diuretics (HR: 1.77, 95% CI 1.31
to 2.38) and prevalent cardiovascular disease (HR: 1.59,
95% CI 1.14 to 2.23), whereas OH hospitalisations
increased with age (HR: 1.11, 95% CI 1.08 to 1.12) and
prevalent diabetes (HR: 1.82, 95% CI 1.23 to 2.70). After
exclusion of 1399 patients with prevalent cardiovascular
disease, a total of 473/464 patients were hospitalised
for unexplained syncope/OH before any cardiovascular
event. Hospitalisation for unexplained syncope predicted
coronary events (HR: 1.85, 95% CI 1.49 to 2.30), heart
failure (HR: 2.24, 95% CI 1.65 to 3.04), atrial fibrillation
(HR: 1.84, 95% CI 1.50 to 2.26), aortic valve stenosis
(HR: 2.06, 95% CI 1.28 to 3.32), all-cause mortality (HR:
1.22, 95% CI 1.09 to 1.37) and cardiovascular death
(HR: 1.72, 95% CI 1.23 to 2.42). OH-hospitalisation
predicted stroke (HR: 1.66, 95% CI 1.24 to 2.23), heart
failure (HR: 1.78, 95% CI 1.21 to 2.62), atrial fibrillation
(HR: 1.89, 95% CI 1.48 to 2.41) and all-cause mortality
(HR: 1.14, 95% CI 1.01 to 1.30).

Conclusions

Patients discharged with the diagnosis
of unexplained syncope or OH show higher incidence of
cardiovascular disease and mortality with only partial
overlap between these two conditions

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Arterial Stiffness in Patients without Hypertension

Ichikawa et al (Ichikawa K, Sakuragi S, Nishihara T, et al. Heart Published Online First: [please include Day Month Year]. doi:10.1136/heartjnl-2017-311751) report a retrospective study examining the relationship between brachial ankle pulse wave velocity (as a measure of arterial stiffness) and coronary artery calcification and cardiovascular events. There are a number of limitations: retrospectivity, importance confounder of age, definition of absence of hypertension (note prevalence of antihypertensives).

Abstract

Objective

Although blood pressure (BP) is a major
determinant of arterial stiffness, whether high pulse
wave velocity (PWV) adversely influences cardiac
parameters and cardiovascular (CV) outcome in patients
without high BP remains unclear.

Methods

Outpatients without high BP (n=320),
defined as systolic BP ≥140 mm Hg, were enrolled in this
retrospective study. At baseline, all patients underwent
echocardiography and multidetector CT to determine the
coronary artery calcification (CAC) score. Arterial stiffness
was assessed based on brachial-ankle PWV (baPWV),
from which patients were classified into two groups:
those with high (≥18 m/s, n=89) and low baPWV (<18
m/s, n=231). Cardiac parameters and CV event incidence
during the follow-up period were compared between
these groups.

Results

In multivariable linear regression analysis,
baPWV was significantly associated with CAC score
and serum N-terminal pro-brain natriuretic peptide
hormone level, after adjustment for confounding factors.
In multivariable logistic regression analysis, baPWV
≥18 m/s was significantly associated with CAC score
≥400 (OR 2.466, 95% CI 1.012 to 6.009, p=0.0471).
Kaplan-Meier analysis showed that the high-baPWV
group experienced more CV events during the 575 days
of follow-up (20% vs 6%, p=0.0003).

Conclusions

High baPWV was associated with greater
CAC and a high risk of a future CV event, especially
coronary artery disease, even in patients without high BP

Heart Failure with Preserved Ejection Fraction Meta-analysis

Zheng et al publish a meta-analysis of therapies for heart failure with preserved ejection fraction.

Abstract

Background

Clinical drug trials in patients with heart failure and preserved ejection fraction have failed to demonstrate improvements in mortality.

Methods

We systematically searched Medline, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCT) assessing pharmacological treatments in patients with heart failure with left ventricular (LV) ejection fraction≥40% from January 1996 to May 2016. The primary efficacy outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, heart failure hospitalisation,exercise capacity (6-min walk distance, exercise duration,VO2 max), quality of life and biomarkers (B-type
natriuretic peptide, N-terminal pro-B-type natriureticpeptide). Random-effects models were used to estimate pooled relative risks (RR) for the binary outcomes, and weighted mean differences for continuous outcomes,
with 95% CI.

Results

We included data from 25 RCTs comprising data for 18101 patients. All-cause mortality was reduced with beta-blocker therapy compared with placebo (RR:
0.78, 95%CI 0.65 to 0.94, p=0.008). There was no effect seen with ACE inhibitors, aldosterone receptor blockers, mineralocorticoid receptor antagonists and other drug classes, compared with placebo. Similar results were observed for cardiovascular mortality. No single drug class reduced heart failure hospitalisation compared with placebo.

Conclusion

The efficacy of treatments in patients with heart failure and an LV ejection fraction≥40% differ depending on the type of therapy, with beta-blockers
demonstrating reductions in all-cause and cardiovascular mortality. Further trials are warranted to confirm treatment effects of beta-blockers in this patient group.

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Off Pump Versus Standard Bypass Surgery

 Shroyer et al report a randomized clinical trial of off pump versus on pump coronary artery bypass surgery (N Engl J Med 2017;377:623-32.
DOI: 10.1056/NEJMoa1614341). There is an accompanying editorial.

ABSTRACT

BACKGROUND

Coronary-artery bypass grafting (CABG) surgery may be performed either with
cardiopulmonary bypass (on pump) or without cardiopulmonary bypass (off pump).
We report the 5-year clinical outcomes in patients who had been included in the
Veterans Affairs trial of on-pump versus off-pump CABG.

METHODS

From February 2002 through June 2007, we randomly assigned 2203 patients at 18
medical centers to undergo either on-pump or off-pump CABG, with 1-year assessments completed by May 2008. The two primary 5-year outcomes were death from any cause and a composite outcome of major adverse cardiovascular events, defined as death from any cause, repeat revascularization (CABG or percutaneous
coronary intervention), or nonfatal myocardial infarction. Secondary 5-year outcomes included death from cardiac causes, repeat revascularization, and nonfatal myocardial infarction. Primary outcomes were assessed at a P value of 0.05 or less, and secondary outcomes at a P value of 0.01 or less.

RESULTS

The rate of death at 5 years was 15.2% in the off-pump group versus 11.9% in the
on-pump group (relative risk, 1.28; 95% confidence interval [CI], 1.03 to 1.58;
P = 0.02). The rate of major adverse cardiovascular events at 5 years was 31.0% in the off-pump group versus 27.1% in the on-pump group (relative risk, 1.14; 95% CI, 1.00 to 1.30; P = 0.046). For the 5-year secondary outcomes, no significant differences were observed: for nonfatal myocardial infarction, the rate was 12.1% in the off-pump group and 9.6% in the on-pump group (P = 0.05); for death from cardiac causes, the rate was 6.3% and 5.3%, respectively (P = 0.29); for repeat revascularization,the rate was 13.1% and 11.9%, respectively (P = 0.39); and for repeat CABG, the rate was 1.4% and 0.5%, respectively (P = 0.02).

CONCLUSIONS

In this randomized trial, off-pump CABG led to lower rates of 5-year survival and event-free survival than on-pump CABG.

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Categories: Uncategorized

Canagliflozin and CV and Renal Events

Neal et al report on Canagliflozin and cardiovascular and renal events (N Engl J Med 2017;377:644-57.DOI: 10.1056/NEJMoa1611925)

ABSTRACT

BACKGROUND

Canagliflozin is a sodium–glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure, body weight, and albuminuria in people with diabetes. We report the effects of treatment with canagliflozin on cardiovascular, renal, and safety outcomes.

METHODS

The CANVAS Program integrated data from two trials involving a total of 10,142
participants with type 2 diabetes and high cardiovascular risk. Participants in each trial were randomly assigned to receive canagliflozin or placebo and were followed for a mean of 188.2 weeks. The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke.

RESULTS

The mean age of the participants was 63.3 years, 35.8% were women, the mean
duration of diabetes was 13.5 years, and 65.6% had a history of cardiovascular
disease. The rate of the primary outcome was lower with canagliflozin than with
placebo (occurring in 26.9 vs. 31.5 participants per 1000 patient-years; hazard ratio, 0.86; 95% confidence interval [CI], 0.75 to 0.97; P<0.001 for noninferiority;P = 0.02 for superiority). Although on the basis of the prespecified hypothesis testing sequence the renal outcomes are not viewed as statistically significant, the results showed a possible benefit of canagliflozin with respect to the progression of albuminuria (hazard ratio, 0.73; 95% CI, 0.67 to 0.79) and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal-replacement therapy, or death from renal causes (hazard ratio, 0.60; 95% CI, 0.47 to 0.77). Adverse reactions were consistent with the previously reported
risks associated with canagliflozin except for an increased risk of amputation
(6.3 vs. 3.4 participants per 1000 patient-years; hazard ratio, 1.97; 95% CI, 1.41 to 2.75); amputations were primarily at the level of the toe or metatarsal.

CONCLUSIONS

In two trials involving patients with type 2 diabetes and an elevated risk of cardiovascular disease, patients treated with canagliflozin had a lower risk of cardiovascular events than those who received placebo but a greater risk of amputation, primarily at the level of the toe or metatarsal.

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Categories: Uncategorized