Two studies on MINOCA
Mileva N, Paolisso
P, Gallinoro E, Fabbricatore
D, Munhoz D, Bergamaschi L
et al. Diagnostic and
Prognostic Role of Cardiac Magnetic
Resonance in MINOCA: Systematic Review and Meta-Analysis. JACC Cardiovasc Imaging 2023;16:376-89. https://doi.org/10.1016/j.jcmg.2022.12.029
Zeng M, Zhao C, Bao X, Liu M, He L, Xu Y et al.
Clinical Characteristics and Prognosis of MINOCA Caused
by Atherosclerotic and Nonatherosclerotic Mechanisms Assessed by OCT. JACC Cardiovasc Imaging 2023;16:521-32.
https://doi.org/10.1016/j.jcmg.2022.10.023
According to the Fourth Universal Definition of Acute Myocardial Infarction (AMI), the term MINOCA designates an AMI (rising and
falling troponins with at least one
value above the 99th percentile, plus at least one of the following criteria: symptoms or ECG changes suggestive of ischemia, development of
pathologic Q waves, evidence
on imaging study, or thrombosis demonstrated on angiography or pathology) in the absence
of obstructive coronary disease ( 50 % lesion in any epicardial
vessel) and other conditions that might justify the condition (sepsis, aortic
dissection, pulmonary embolism,
myocarditis, Takotsubo, etc.). The mechanisms
responsible may involve the epicardial vessels (spasm, thrombosis in situ, embolism, dissection) or the microcirculation
(spasm or microvascular dysfunction). Although the prognosis is better than
that of AMI with epicardial coronary disease, it is far from benign, and the recurrence of symptoms is high.
The diagnosis of MINOCA has been defined as a “working diagnosis”, since, as can be seen
from the definition, after demonstrating the absence of obstructive coronary
artery disease on coronary angiography,
progress must be made in ruling out alternative causes of the clinical picture. At the time of the suggested
diagnostic studies, the Argentine Consensus of
MINOCA (Rev Argent Cardiol 2022;90: supl. 2) proposes the assessment of wall motion, invasively
with angiographic ventriculography
or non-invasively with a Doppler
echocardiogram (both studies with IB indication), which help to approximate the
diagnosis by defining whether there is a regional alteration (more in favor of a diagnosis of MINOCA) or global,
if there is the presence
of dissection, cardioembolism (if in doubt,
transesophageal echocardiography
can be used), etc. In the diagnostic
algorithm, cardiac magnetic resonance (CMR) appears
next, also with IB indication, for all cases in which diagnostic doubts arise.
Demonstration of an ischemic patent
on CMR will confirm the diagnosis of MINOCA.
Although it is increasingly used, CMR has different strength of indication in
different guidelines, and its place in the order of studies
varies according to the availability of the resource,
costs, etc.
We have just learned about
a systematic review
and meta-analysis of
published studies on the diagnostic and
prognostic yield of CMR in the context of the MINOCA presumptive case study.
Studies that reported
the results of a CMR performed within 10 days of the index event in patients with a “working
diagnosis” of MINOCA, and in which the prevalence, beyond confirmation of the presumptive diagnosis, was included
of alternative diagnoses: AMI, myocarditis, Takotsubo,
or a normal result. A total of 26 studies were included, with 3624 patients, 56%
men, with a mean age 54 years. 11% had diabetes, 31% arterial hypertension, 32% dyslipidemia, and 24% were smokers. CMR was performed at a median of 6 days (interquartile range,
IQR, 2-9 days). The definitive
diagnosis was Takotsubo in 10% of the cases (95% CI 6-12%), myocarditis in 31% (95% CI 25- 39%);
there were other alternative diagnoses (dilated, hypertrophic, or arrhythmogenic
cardiomyopathy) in 10%, and the
findings were normal in 27% of cases (95%
CI 18-38 %). And the MINOCA? A patent suggestive of AMI was seen in 22% of the studies
(95% CI 17- 26%),
that is, the MINOCA condition was confirmed in
one out of every 5 cases. Something
that deserves to be highlighted is the high degree of heterogeneity between the different studies in the prevalence
of each of the diagnoses mentioned,
which for Takotsubo, myocarditis and MINOCA was
around 90%. In 5 studies (770 patients,
median follow-up 45 months) it was possible
to define the prognostic value of CMR findings: while the diagnosis of myocarditis or Takotsubo did not imply a far worse prognosis
(OR of 1.09 and 1.16 respectively, in both cases with p=NS), that of MINOCA
was associated with a higher risk of major
adverse cardiovascular events (OR 2.40, 95% CI 1.60-3.69).
Based on the findings of their meta-analysis, the authors propose a
diagnostic algorithm, in which, in patients with a presumptive diagnosis of
MINOCA (coronary angiography or coronary CT angiography without
evidence of obstructive disease), after having
ruled out extracardiac
causes of increased troponin (dissection, sepsis,
pulmonary embolism, etc.), the immediate step is to perform CMR. The demonstration of
an ischemic patent (by compatible
findings of late gadolinium enhancement, T1/T2
mapping and alteration of the extracellular volume)
certifies the diagnosis, and enables, if necessary, to carry out invasive
studies that clarify the causal
mechanism: intracoronary ultrasound, intracoronary vasoreactivity
test, optical coherence tomography (OCT), etc. A non-ischemic patent suggests Takotsubo, myocarditis, other cardiomyopathies. A normal patent (more than a quarter of the cases in the
meta-analysis) leaves the condition without a clear diagnosis.
As we said, the pathophysiology underlying MINOCA is
variable. AMI may be due to atherosclerotic mechanisms (mainly
plaque rupture or erosion, or calcified nodule) or non-atherosclerotic
mechanisms (vasospasm, spontaneous coronary dissection, or microvascular
dysfunction). Among the diagnostic methods that
serve to clarify the point is OCT. A recent publication serves to differentiate
the prognostic value of the
aforementioned mechanisms. It is a single-center study with retrospective analysis of data collected prospectively in a center in China.
Between January 2016 and December
2019, 7423 patients
were admitted with a
diagnosis of AMI and studied with coronary angiography. MINOCA was diagnosed in
294 according to the aforementioned criteria. Of these, 190 underwent OCT.
The study could not be performed in patients with complex and tortuous coronary anatomy, renal dysfunction, or hemodynamically unstable. Of the 190 patients with
OCT, 99 (52%) were diagnosed with atherosclerotic mechanisms responsible: plaque erosion in 64 (33.7%), rupture
in 33 (17.4%), and calcified
nodule in 2 (1.1%). Non-atherosclerotic mechanisms were diagnosed in the
remaining 91 patients (48%): dissection in 8 (4.2%), spasm in 9 (4.7%), and the
cause could not be classified in 74 (38.9%). Compared with their counterparts, patients with atherosclerotic mechanisms
were more frequently men, smokers,
with ST-segment elevation AMI and
higher troponin values. In them, the presence
of arteries with <30% lesion
was less frequent,
and the finding of arteries with lesions between 30 and 50% was more prevalent. Regarding the lesions
considered to be responsible for
the condition, in the cases of atherosclerotic mechanism
the area of stenosis was larger, the lesions were longer, the fibrous cover of the plaques was thinner, and the lipid content was
higher. Thrombus was observed in 86% of patients with an atherosclerotic
mechanism and in none of the others. These differences were replicated in the non-culprit arteries.
Follow-up data were available for 187 patients at a median
of 720 days. In the first year, patients with atherosclerotic mechanisms experienced 15 major cardiovascular adverse events (15.3%):
2 cardiac deaths (2%),
6 culprit lesion revascularization procedures (6.1%), 1 ischemic stroke (1 %) and 6 readmissions
for progressive angina (6.1%). Patients with non-atherosclerotic mechanisms experienced only 4 major
cardiovascular adverse events (4.5%):
3 cardiac deaths (3.4%) and 1 non-fatal
AMI (1.1%), all in patients with a cause not
specified by the OCT.
These
two publications contribute to unraveling the
causal mechanisms and strengthening a diagnostic strategy in the field of AMI with non-obstructive coronary
artery disease. The first is a large meta-analysis. The diagnosis of
MINOCA is of increasing incidence. This is mainly
due to 2 conditions: the expansion of the use of troponin as a diagnostic tool, which leads to increased detection, and a greater awareness of its relevance
and prognostic significance. The almost
systematic performance of coronary angiography in the
presence of an increase in troponin and a compatible condition leads to a more frequent diagnosis of
this type of condition. At the same
time, the use of CMR is growing as a study that makes it possible to define precise patents to differentiate ischemic and non-ischemic conditions when doubts about the coronary origin persist. One merit of this meta- analysis is that it included only
studies in which CMR was performed
within the first 10 days, thus avoiding the loss of sensitivity that occurs when carrying out the studies late, when the initial findings fade. It is relevant to take into account some findings. First,
that MINOCA was confirmed in only one fifth of the
cases; this confirms the criterion of the concept of “working diagnosis” and reveals how close in their presentation are pictures of different etiology and pathophysiology. It is true that when coronary
angiography accurately indicates the image of a <50% lesion that seems to be responsible for the episode, other studies often do not advance; so it is possible
that many MINOCAs have not then reached CMR,
which dilutes their prevalence. within the compatible
boxes. Second, the reaffirmation that MINOCA
is not a trivial condition: compared to myocarditis and Takotsubo, it is associated with a worse prognosis, so an
accurate initial diagnosis is essential to implement measures that contribute to improving evolution
in time and prevent future events. Third, that in this line it is regrettable that almost a third of the cases remained undiagnosed;
the publication does not clarify the prognosis for this group, who had symptoms compatible with AMI and whose mechanism was unknown (it is not innocuous
to have troponin elevation). Fourth, the idea of supporting CMR as a central diagnostic method seems attractive: the information it provides is extremely rich; but let us take into account this third
of undiagnosed patients, the high heterogeneity between the publications on the proportion of each of the diagnoses out of the total (for example, the 95% CI of normal findings ranges
from 18% to 38%) and the limitations on the availability of the resource
in many media. If we have CMR, its use in cases like these seems indicated, although it does not provide absolute certainty in all cases; if we do not have it, we must use all the means at our
disposal to clarify the responsible mechanism. It is not of little importance to
thoroughly review the initial
coronary angiography: more than once the repeated
examination allows to detect thrombi, dissections, lesions, unnoticed
in the first observation.
The second study follows the same line as the previous one, in this case using a less widespread diagnostic method in our setting, OCT. It focuses
on patients in whom the diagnosis
of MINOCA has already been made (myocarditis, Takotsubo,
etc. have already been excluded). Atherosclerotic and non-atherosclerotic mechanisms appear equally
distributed. Logically, pictures
of atherosclerotic origin share clinical and
pathophysiological characteristics with traditional obstructive coronary
disease: a higher prevalence
of men, smokers, ST-segment elevation
AMI, plaques rich in lipids and with a thin coating, more predisposed to rupture, thrombosis.
Although by definition they are <50%, the presence of lesions between
30% and 50% is higher
in this group.
It seems that in these patients there is simply a question
of degree with obstructive coronary artery disease. On the other
hand, what generates more doubts is the counterpart of patients in whom a non-atherosclerotic mechanism is
diagnosed. Perhaps the term
“diagnostic” is too ambitious: it can only be affirmed that there is no demonstration of the phenomena of the previous group in the OCT, but in 74 of the 91, more than 80%, there is no defined mechanism
that has led to the MINOCA,
and this is striking. The lack of systematic CMR raises a question: are there not clinical entities
among these patients
that this study
would have contributed to diagnose? Are all these
patients truly MINOCA? The authors
maintain that in half of these cases,
characteristics of the angiographic study suggested microvascular disease; even so, more than 30 patients remain in the nebula. And to be honest, there is a previous doubt:
of the 294 initial patients, in more than a third the OCT was not carried out. It is not explicit
why, nor if these patients
had differential characteristics, which makes the conclusions of the study somewhat less certain. What is clear is that the presence of atherosclerotic mechanisms indicates a worse prognosis, and that the not so fearsome evolution of MINOCA that has been cited so many
times is probably the expression of a mixture of patients with different processes involved. In this sense, the
pathophysiological information
provided by OCT is notable, as well as the limitation
for its use in daily practice for logistical and access reasons.
One
last comment: the 74 patients without a definite diagnosis with OCT, 38% of the total, remind us of the 27% of CMR with normal findings from the
previous study: each method has its limitations. It seems that more
than one diagnostic resource is necessary for an accurate definition. We repeat, going back to see the initial
coronary angiography in detail should be the rule.
How fast does aortic
stenosis progress? Revealing data from a meta-analysis
Willner N, Prosperi-Porta G, Lau L, Nam
Fu AY, Boczar K, Poulin A et al. Aortic
Stenosis Progression: A Systematic Review and Meta-Analysis. JACC Cardiovasc Imaging 2023;16:314-28. https://doi.org/10.1016/j.jcmg.2022.10.009.
Aortic stenosis (AS) is the most prevalent valve disease in the West. Its prevalence increases with age, and when it reaches severity criteria, the
only therapeutic solution
is valve replacement, surgical or percutaneous. A common problem that arises in daily practice is being able to predict, when faced with a
patient with mild or moderate AS,
in what time it will become severe. The information
in this regard is scattered and sometimes contradictory.
The question has become more important since randomized studies have indicated
that invasive treatment is associated with a better prognosis
in advanced conditions regardless of the presence of symptoms.
In this sense,
the publication of a systematic review and
meta-analysis of prospective studies with follow-up of at least 12 months in
which the severity of the disease and
its annual progression were evaluated in patients
with AS, with the use of echocardiographic parameters,
is extremely useful: mean gradient (MG), peak
gradient (PG), peak velocity (PV), or aortic valve area (AVA);
or computed tomography, with determination of a valve calcification score.
After an exhaustive selection process, 24 studies with 5450 patients, with mean age 68 years,
60% men, were considered for analysis. Mild AS was defined as that with a MG < 20 mm Hg, a PG < 36 mm Hg, a PV of 2.5-3 m/s, or an AVA > 1.5 cm2; as moderate AS, those with MG 20-40 mm Hg, PG 36-64 mm Hg,
PV 3-4 m/s or an AVA 1-1.5 cm2; and
as severe AS, those with MG > 40 mm Hg, PG > 64 mm Hg, PV > 4 m/s or AVA
< 1 cm2 . Regarding
valve calcification, mild AS was considered if the calcium score was
<500 AU, moderate
AS with values between 500 and 1500, and severe AS with values >1500 AU.
When considering MG as the baseline parameter to classify the severity of AS, a mean rate (95% CI) of annual progression of said parameter of
2.3 (0.9-3.7) mm Hg was observed in
mild AS, 4.3 (3.2-5.7) mm Hg in
moderate AS and 10 (9-11) mm Hg in severe AS
(p<0.001 for the difference in progression according
to baseline severity,
although with high heterogeneity in the results).
Considering PV as the baseline
parameter, the average rate (95% CI) of annual
progression of this parameter was 0.09 (-0.04-0.21) m/s in mild AS; 0.18
(0.12-0.23) m/s in moderate
AS and 0.33 (0.21-0.46) m/s in severe AS (p=0.001 for the difference in progression according to basal severity, although also with high heterogeneity).
In the case of the PG, the annual changes were
respectively 5.7 (0.09-11.3) mm Hg, 6.6 (5-8.3) mm Hg and 15 (12-17.9) mm Hg. The heterogeneity was high, but no significant difference could be demonstrated according to baseline severity, due to the similarity of progression between the mild and moderate forms.
Something similar happened in the case of AVA: the annual fall was almost identical
between mild and moderate
AS: -0.07 (-0.10 to -0.05) cm2 and -0.08 (-0.10
to -0.06) cm2 and higher in severe AS: -0.12 (-0.16 to-0.07) cm2.
Regarding the calcium score, there was a significant difference according to the baseline severity
of AS, with mean annual
increases of 101, 202, and 323 AU in mild,
moderate, and severe AS.
The results of this meta-analysis have practical utility.
They indicate the expected rate of progression for
each parameter of hemodynamic or anatomical severity
of AS, according
to its severity at the time of the initial
examination. It is clear that the most challenging clinical problem we
face on a daily basis in this regard
is the time it can take for moderate
AS to progress to severe AS. In this sense,
considering the upper
end of the 95% CI for gradients and speed, and the
lower end for AVA (which implies
the greatest drop), we can estimate this time. For example, in the case of
PV, in moderate AS the upper end of the 95% CI in the annual rate of progression is 0.23 m/s. Getting from 3 m/s (moderate AS) to 4.1 m/s (severe AS) can take a minimum of almost 5 years: (4.1-3)
/0.23. Of course, these data are
estimates: they are a summary
measure of change, summarizing the information from large numbers of individual patients
into a single number. Individual baseline characteristics are not taken into account.
For example, in a patient
with chronic kidney disease in advanced stages, with an increased incidence of calcification processes, the times are surely
shortened substantially.
In
the case of echocardiographic parameters, it is noteworthy that only the rate of progression of MG and PV is different
depending on the initial severity.
The authors maintain that
this is due to the fact that the calculation
of the PG amplifies the error that may have occurred in the measurement of the PV, since PG=4 (PV) 2; and that the determination of
the AVA (although essential when
defining the severity of the AS) is subject to methodological issues that may vary according
to the operator and the technique. In any case, the high heterogeneity of the findings in each of
the parameters explored should be highlighted,
which makes the summary value more of a global expression than a determination
that we can apply with absolute certainty. The
final message is perhaps something that we intuitively apply in daily practice: the closer a
condition is to advanced stages that require taking extraordinary measures, the closer follow-up and more frequent
diagnostic studies should be implemented.
Meta-analysis of TAVI vs Surgical
Valve Replacement: Differences in Outcomes by Baseline Risk
in Randomized Trials
Ahmad Y, Howard JP, Arnold AD, Madhavan MV, Cook CM, Alu M et al. Transcatheter versus surgical aortic valve replacement in lower-risk and higher-risk patients: a
meta-analysis of randomized trials. Eur Heart J 2023;44:836-52. https://doi.org/10.1093/eurheartj/ehac642.
Since its inception, transcatheter
aortic valve implantation (TAVI) has played an increasing role in the treatment
of severe AS. Initially tested in inoperable
patients vs. medical
treatment was later compared with surgical valve replacement (SAVR) in
high-risk surgical patients, and then
in lower-risk patients. The demonstration of non-inferiority with respect to SAVR, with shorter hospitalization times and a
reduction in a series of
complications, gave TAVI a clear place in the
treatment of AS. As with any new technology, the necessary learning
curve, and cost and effectiveness issues also
influence the decision to go ahead. An objection usually made is related to the follow-up
time of the studies, often judged
insufficient to define
durability of the implant and long-term results.
We are now aware of a meta-analysis that considered only randomized studies (excluding observational studies)
that compared TAVI with SAVR, with a minimum follow-up of 1 year. It has the virtue of incorporating
the maximum follow-up reported so far from each study. The main outcomes were all-cause mortality, all strokes,
and the composite of death or disabling
stroke, as reported in each
trial. Secondary endpoints included cardiac (or cardiovascular) death,
disabling stroke, AMI, permanent
new pacemaker implantation,
aortic valve reoperation, major bleeding, major vascular complications, paravalvular leak,
occurrence of atrial fibrillation
(AF), rehospitalization and the incidence of acute
kidney injury (AKI)
Eight studies were included, divided
by the baseline risk of
the patients, according to the STS-PROM score (Society
of Thoracic Surgeons
score for predicting mortality) into low- and high-risk studies. For each study, subsequent publications to the original
that updated data on long-term
survival were also considered. Low- risk studies
were those with an STS-PROM
score < 4%: PARTNER 3, Evolut Low-Risk,
NOTION, and UK TAVI. The mean age in these
studies ranged from 73 to 81 years. High-risk studies (STS-PROM
> 4%) were PARTNER 1A, CoreValve High-Risk, PARTNER 2, and SURTAVI. The mean age in this case ranged from
79.8 to 84 years. In total, 8698 patients were treated, 3557 low risk, 5141 high risk; 4443
assigned to TAVI and 4255 to SAVR.
The maximum duration of follow-up available for this analysis was 1 year in one
trial, 2 years in two trials,
5 years in four trials,
and 8 years in one trial.
The weighted mean duration of follow-up was almost
4 years, 46.5 months. The risk ratio
for early events (within the
first year of follow-up) between TAVI
and SAVR was expressed as RR, and after the first
year and globally as HR, in both cases with their corresponding 95% CI.
When considering death from all causes as the endpoint, in the four low-risk studies,
the RR with TAVI compared to SAVR within the first year was 0.67 (95%CI 0.47-0.96), p=0, 03. At longer-term
follow-up, the HR was 0.90 (95% CI 0.69-1.17), p=NS. Assessing
total follow-up duration with a meta-analysis of reconstructed individual data, there was no significant difference, but a trend, in all-cause
mortality between TAVI and SAVR (overall
HR 0.79, 95% CI 0.60–1.04, p
= 0.09),
with significant heterogeneity in the results,
and with a difference in mean survival between the two strategies of only 0.8 months, not
significant: 54.3 vs 53.5 months. In the four highest-risk trials, the RR within the first year was 0.93 (95% CI
0.81–1.08), and the longer-term HR
was 1.04 (95% CI 0.96–1.13), in both
cases with p=NS. In these trials the proportional hazards changed over time. There was a lower risk of
death with TAVI up to 6 months (HR 0.68, 95%CI
0.56-0.82, p<0.01), but higher risk beyond 6 months (HR 1.17, 95% CI 1.05-1.29, p<0.01). When evaluating the total duration of follow-up, there
was no difference between the two groups (OR 1.07, 95% CI 0.95-1.20, p=
0.27), with a difference in mean survival of only 0.5 months, not significant (46.2 vs. 45.7 months).
Regarding the stroke endpoint, in the four low-risk trials, the RR of TAVI relative to SAVR
was 0.91 (95% CI 0.46-1.80), and at longer follow-up term, the HR was
0.93 (95% CI 0.66–1.31), in both cases with p=NS. In the four highest-risk trials, the
situation was analogous: the RR at one year was 0.93 (95%CI 0.68-1.27), and the HR after one year was 0.94 (95%CI 0.75-1.18), also with p=NS in both cases. When
evaluating the total follow-up duration
for each trial as a whole with the meta-analysis of reconstructed individual
data, there was a lower risk of stroke
with TAVI up to 3 months for the
low-risk studies (HR 0.52, 95% CI 0 0.30-0.88) but higher risk later (HR 2.14, 95% CI 1.22-3.78), without significant differences when evaluating
global follow- up (OR 1.03, 95% CI 0.71- 1.49, P = 0.87). For the high- risk trials, there was no difference in
stroke risk up to 3 months (HR 0.87,
95% CI 0.68–1.12) and thereafter (HR 1.06, 95% CI 0.82-1.37).
The composite endpoint death or disabling stroke reproduced the trends indicated when talking about all- cause mortality. In low-risk studies, the
RR up to one year was 0.68 (95% CI
0.50-0.92), p=0.01; and the HR after
one year 0.85 (95% CI 0.63-1.15), p=NS. Overall, the HR was 0.85 (95% CI 0.67-1.08). In high-risk studies, the RR
after one year was 0.90 (95% CI 0.79–1.02)
and the HR after one year was 1.04 (95% CI 0.96–1.13), always with p=NS. When considering the incidence of events at 6 months instead of 1 year, a
dual behavior was again seen: at 6
months risk reduction, with HR 0.73 (95% CI 0.62–0.85), p < 0 .01), and then increased
risk, with HR 1.20 (95% CI 1.09–1.33), p < 0.01. When
evaluating the total duration of follow-up, there was no significant difference between the two groups (OR 1.09, 95% CI: 0.97–1.23, p = 0.12),
with a small difference in event-free survival, 44.8 vs. 44.4 months.
Regarding secondary endpoints, assessed up to 1 year of follow-up, in the low-risk studies
there was no significant difference
between TAVI and SAVR for AMI and
valve reoperation. TAVI was associated with increased need for a new permanent pacemaker and mild to moderate paravalvular leak and major vascular complications, but with lower risk of
disabling stroke, cardiac death (borderline statistical significance, p=0.05), rehospitalization,
AKI, AF and major bleeding. In the higher-risk
studies, there was no significant difference
between the two strategies for cardiac death, MI, or disabling
stroke, but, as in the low-risk studies, greater need for permanent pacemaker, aortic valve reoperation, mild paravalvular leak and moderate and major vascular complications; and reduction of
new AF, AKI, or major bleeding.
This
meta-analysis offers us the longest follow-up
to date, based on all available sources
and updates, of the total number of randomized TAVI vs. SAVR studies carried out to date. Initially emerging as a therapeutic alternative in patients with inoperable AS or high surgical risk, the practice
of TAVI has been expanding, as is the case with many other treatments, to less serious
conditions. Thus, for example, the annual mortality in the PARTNER 1A study in 2011 was 24.2% in the TAVI group and 26.8% in the
SAVT group; in the PARTNER
2 study in 2012, 12.3% with TAVI and
12.9% after SAVR; and in the PARTNER
3 trial, in low-risk patients in 2019,
1.0% with TAVI and 2.5% with SAVR.
As relevant
results, we can conclude that, in studies
with low-risk patients, there is, with TAVI compared
to SAVR, a reduction in the
risk of death in the first year, and of death plus disabling
stroke. Considering only the effect
on stroke, a risk reduction
is verified only up to 3 months,
but it increases afterwards, so the effect after one year is neutral. In extended follow-up, the effect on total mortality is attenuated, and is restricted to a trend.
What are also the advantages for TAVI? Less disabling
stroke as an individual event, arrhythmias, bleeding, and AF, and a strong
downward trend in cardiac mortality. The price to pay? Increased need for valve reoperation, vascular complications, and permanent pacemaker implantation.
What happens
in high-risk trials?
We see a reduction in the risk of death or death plus disabling stroke
only in the first 6 months, with an increase
thereafter, so that the final effect after one year is neutral. The effects
on secondary points are similar
to those in low-risk studies.
Events that occur more frequently after TAVI (paravalvular leak, reoperation, need for permanent pacemaker) impact longer-term prognosis; those with greater frequency after SAVR (bleeding, AF, AKI, disabling
stroke) are of greater relevance in the short term. This
may explain the initial advantage for TAVI compared to SAVR
on total mortality, evident up to 1 year in
low-risk trials and only up to 6 months in high-risk trials,
in which a rebound effect
is then verified, which neutralizes the initial
advantage when we extend to the year.
Therefore, contrary to the widespread belief that TAVI offers a net benefit in survival compared to SAVR in patients at higher risk, it can be deduced
from this analysis
that the advantage
seems to lie in patients
who are not so compromised. And, in any case, the difference in event-free survival between the two treatments never exceeds
one month. The statistical significance then
seems more striking than the clinical one.
As
limitations we can mention that we are dealing
with a meta-analysis formulated at the study level, not individual data. The authors refer to
“reconstructed individual data”: this is a technique that infers information from survival graphs,
Kaplan Meier curves;
there is no true availability
of individual patient data. Something that should be highlighted is the high
degree of heterogeneity between
the studies (significant differences in many of the results), so the summary measure of effect should be seen as suggestive but not as certainty of the magnitude
of a particular effect.
Finally,
this meta-analysis is of randomized studies,
with all due considerations for high internal
validity and more debatable external validity. Different
national and international registries can contribute to a more complete picture of reality, with the
inherent risk of the presence of
confounders beyond those known. An extension of the follow-up periods of the aforementioned studies, data from new clinical trials
and registries will contribute to a more complete knowledge of what we can expect
from TAVI in our patients with severe AS in the longer term (further prognosis, implant longevity, etc.) Meanwhile, the development of the technique and its use grow incessantly.
Socioeconomic differences and evolution of AMI in 6 high-income countries
Landon BE, Hatfield LA, Bakx P, Banerjee A, Chen
YC, Fu C et al. Differences in Treatment
Patterns and Outcomes of Acute Myocardial Infarction for Low- and High-Income Patients
in 6 Countries. JAMA 2023;329:1088-97. https://doi.org/10.1001/jama.2023.1699.
It is generally recognized that socioeconomic differences translate into a different cardiovascular risk profile of patients, a different degree of coverage, dissimilar access to the health
system and use of resources, and, presumably, a different prognosis. It is clear that the evolution of the patients
differs between rich and poor countries. But what happens when we focus on rich countries with wide health coverage? Does the socioeconomic level influence the fate of patients? We present a collaborative study conducted in 6 high-income countries: Taiwan, the Netherlands, England, the United States
of America, Canada (Ontario and
Manitoba), and Israel. This is a retrospective analysis of administrative databases, with the analysis of information on patients 66 years of age or older, hospitalized for an AMI with ST-segment elevation (STEMI) or without ST-segment elevation
(NSTEMI). In the case of the United
States, these were Medicare patients.
The period between the beginning of 2013 and the end of 2018 was analyzed. The data of
the patients whose dwelling (defined from the zip code) corresponded to the location of the highest 20% and the lowest 20% of the income distribution were considered in each region. The primary end point was 30-day and 1-year mortality, adjusted for age, sex, and comorbidities; and secondary end points the use of coronary angiography, and the performance
of angioplasty and coronary surgery. Patients who had had an AMI in the year prior to the index hospitalization were excluded.
A total of 289 376 hospitalizations for STEMI and 843 046 with NSTEMI were analyzed. The
income ratio between rich and poor patients ranged from 1.35 in
Taiwan to 4.36 in Israel. The incidence of both AMI types was higher among the lowest-income patients
in all 6 countries; the most striking
differences were seen in
Israel, with annual STEMI incidence of 2.1 ‰ in the poorest 20‰ and 1.1 ‰ in the richest 20%, and corresponding figures of 4.8 ‰ and 2.3 ‰ for NSTEMI.
The incidence of hard events was higher among the poor.
With regard to STEMI, the most notable
difference in 30-day mortality was
seen in Canada (2.9% excess), while
in Taiwan it was practically nil; in mortality at one year, the greatest excess mortality among those with lower incomes
was seen in Israel (9.1%),
while in Taiwan again it was around 0. Regarding
NSTEMI, in 30-day mortality the most notable
difference was seen in
Israel (2.8% excess among the poor) and something similar occurred at 1 year (6.7% excess) while in Taiwan there were no significant differences between poor and rich at 30 days or 1 year.
For cardiac catheterization, the utilization rate was
also higher among wealthier patients in all cases, with the greatest
difference in England
(5.9% excess in STEMI and 9.6% in NSTEMI), and the lowest
in Taiwan (2.4% and 1.7% respectively). And for coronary angioplasty, again the biggest difference
was seen in England (6.1% and 6.5%
for STEMI and NSTEMI) and the
smallest in the Netherlands for STEMI (3.3%). and in Taiwan for NSTEMI (1.6%). The length of stay was shorter
for wealthier patients, except in Israel
and Taiwan, and the 30-day
readmission rate was also lower for higher-income patients.
This analysis delivers a series
of interesting conclusions. Even in rich countries with good health
systems, socioeconomic
differences appear to be associated with different rates of resource utilization and
evolution of AMI in different socioeconomic strata. It is nonetheless interesting that the country with the least inequality (Taiwan) appears as the one with no difference in mortality from AMI at 30 days and one year;
and that the country with the greatest difference in income between rich and poor (Israel) is the one with the greatest difference in mortality for STEMI at one year, and for NSTEMI at 30 days and one year. There is, it is true, no absolute
correspondence between the differences in the indication for catheterization and angioplasty and the differences in mortality: England appears as the country
with the greatest
discrepancy in the use of catheterization and angioplasty between rich and poor for both types of AMI, but it is not for this is the one with the greatest difference in mortality (even for STEMI it is in fourth place among the 6 considered). The poor not only have higher mortality
in general: their length of stay time is longer, and their readmission rate is higher, in all
countries. This suggests that
other factors, beyond revascularization, influence the long-term prognosis. Despite adjusting for age and comorbidities, other
factors undoubtedly play a role. And in this sense, it is regrettable that this analysis does not consider, for example, the differences in outpatient drug treatment. We do not have data on antiplatelet drugs, statins, and neurohormonal antagonists; surely part of the differences in the prognosis
of the patients go beyond what
happens to them in hospitalization: complete medical treatment, frequency of follow-up visits, easier
access to the consultation, adequate compliance with diet, recreation and physical activity, are all factors
that we know differ between
poor and rich and undoubtedly also define their prognosis.
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©Revista
Argentina de Cardiología