This study has already been inappropriately quoted in the media which is what the public read and misinformation is propagating. The authors need to take some responsibility for failing to point out that the dosing of the statins prescribed (most likely archaic low dose simvastatin) isn't analysed and long term compliance isn't addressed in this ' primary prevention population based longitudinal non interventional study'
Cardiologists are going to inundated with questions from patients with coronary disease on statins who have misinterpreted information which is incomplete and misrepresented - the title of the study needs to be highlighted 'Initiation of statins' is well put and needs to be remembered. The study cannot address the 'ongoing management' of cardiovascular risk with appropriate cardiovascular investigation of patients and optimization of preventative strategies as this study does not address this crucial aspect.
It is already well proven that only moderate to high dose statin therapy has a proven biological anti-atherogenic effect so that low doses initiated in general practice are actually ineffective and this is what the study shows NOT that statins are ineffective but that medical practice of blanket prescribing of low doses of statins is ineffective without monitoring of response and ongoing titration to achieve evidence based targets. This omission from the conclusions needs to be corrected and it ne...
This study has already been inappropriately quoted in the media which is what the public read and misinformation is propagating. The authors need to take some responsibility for failing to point out that the dosing of the statins prescribed (most likely archaic low dose simvastatin) isn't analysed and long term compliance isn't addressed in this ' primary prevention population based longitudinal non interventional study'
Cardiologists are going to inundated with questions from patients with coronary disease on statins who have misinterpreted information which is incomplete and misrepresented - the title of the study needs to be highlighted 'Initiation of statins' is well put and needs to be remembered. The study cannot address the 'ongoing management' of cardiovascular risk with appropriate cardiovascular investigation of patients and optimization of preventative strategies as this study does not address this crucial aspect.
It is already well proven that only moderate to high dose statin therapy has a proven biological anti-atherogenic effect so that low doses initiated in general practice are actually ineffective and this is what the study shows NOT that statins are ineffective but that medical practice of blanket prescribing of low doses of statins is ineffective without monitoring of response and ongoing titration to achieve evidence based targets. This omission from the conclusions needs to be corrected and it needs to be emphasized that patients with cardiovascular disease on proper high dose statins are not part of this study at all.
The conclusion of this article was twofold: 1) approximately half of primary care patients put on statins did not achieve at least a 40% reduction in LDL-Cholesterol (the sub-optimal group) and 2) those who did (the optimal group) had fewer cardiovascular incidents over the next (approximately six) years.
Table 1 in the paper shows that the sub-optimal group have 1.43 times the “alcohol misuse” of the optimal group. There is no more information on alcohol consumption beyond this. Were the alcohol misusers also far less likely to be non or moderate drinkers and far more likely to be heavy and frequent drinkers?
The smoking information shows that, from the limited information available, the sub-optimal group were 25% more likely to be smokers. However, there is no smoking information for 96% of patients. There is no activity information – were the drinking/smokers more likely to be sedentary? Were they more likely to be obese?
There were more men in the sub-optimal group. The sub-optimal patients were more likely to be poorly-controlled diabetics and less likely to have hypertension treated.
Correspondence with the researchers confirmed that the HRs in Table 2 were not adjusted for anything other than age and baseline LDL-Cholesterol. They were not adjusted for alcohol misuse, or smoking, or gender, or any other lifestyle factors that were known to be different between the two groups – even with vast amounts of missing information.
The conclusion of this article was twofold: 1) approximately half of primary care patients put on statins did not achieve at least a 40% reduction in LDL-Cholesterol (the sub-optimal group) and 2) those who did (the optimal group) had fewer cardiovascular incidents over the next (approximately six) years.
Table 1 in the paper shows that the sub-optimal group have 1.43 times the “alcohol misuse” of the optimal group. There is no more information on alcohol consumption beyond this. Were the alcohol misusers also far less likely to be non or moderate drinkers and far more likely to be heavy and frequent drinkers?
The smoking information shows that, from the limited information available, the sub-optimal group were 25% more likely to be smokers. However, there is no smoking information for 96% of patients. There is no activity information – were the drinking/smokers more likely to be sedentary? Were they more likely to be obese?
There were more men in the sub-optimal group. The sub-optimal patients were more likely to be poorly-controlled diabetics and less likely to have hypertension treated.
Correspondence with the researchers confirmed that the HRs in Table 2 were not adjusted for anything other than age and baseline LDL-Cholesterol. They were not adjusted for alcohol misuse, or smoking, or gender, or any other lifestyle factors that were known to be different between the two groups – even with vast amounts of missing information.
The entire differences between the groups for CVD events were credited to statins/the degree of cholesterol-lowering. None to lifestyle differences. This should be corrected, as it is wrong and misleading.
In their prospective cohort study of 165,411 primary care patients, Akyea et al. claim that suboptimal responders on statin treatment will experience significantly increased risk of future cardiovascular disease (CVD)(1). As many cardiovascular events may heal without serious health problems, we consider mortality as the most important outcome. Among the 80,802 patients with optimal cholesterol lowering, 821 (1.01 %) died from CVD. Among the 84,609 patients with suboptimal cholesterol-lowering 873 (1.03 %) died. This means that to prevent one cardiovascular death by optimal cholesterol lowering you have to increase the degree of lowering in 5,000 patients for six years. This is hardly a benefit because several independent researchers have reported that serious side effects from statin treatment are much more common than reported in the statin trials (2). The small numbers reported in the trial reports are achieved by excluding participants who suffer from side effects of the drug during a few weeks long run-in period before the start of the trial. That this is an effective method to lower the number of side effects appeared in the IDEAL trial where this method wasn´t used and where a high statin dose was compared with a low dose, because in that trial almost half of the participants in both groups suffered from serious side effects (2).
Furthermore, Akyea et al. have not reported total mortality in the two groups. This failure may introduce another bias because tota...
In their prospective cohort study of 165,411 primary care patients, Akyea et al. claim that suboptimal responders on statin treatment will experience significantly increased risk of future cardiovascular disease (CVD)(1). As many cardiovascular events may heal without serious health problems, we consider mortality as the most important outcome. Among the 80,802 patients with optimal cholesterol lowering, 821 (1.01 %) died from CVD. Among the 84,609 patients with suboptimal cholesterol-lowering 873 (1.03 %) died. This means that to prevent one cardiovascular death by optimal cholesterol lowering you have to increase the degree of lowering in 5,000 patients for six years. This is hardly a benefit because several independent researchers have reported that serious side effects from statin treatment are much more common than reported in the statin trials (2). The small numbers reported in the trial reports are achieved by excluding participants who suffer from side effects of the drug during a few weeks long run-in period before the start of the trial. That this is an effective method to lower the number of side effects appeared in the IDEAL trial where this method wasn´t used and where a high statin dose was compared with a low dose, because in that trial almost half of the participants in both groups suffered from serious side effects (2).
Furthermore, Akyea et al. have not reported total mortality in the two groups. This failure may introduce another bias because total mortality was higher in at least seven
statin trials (AFCAPS/TEXcaps, ASPEN, TNT, SPARCL, DEBATE, SEAS and GISSI-HF) (2).
A relevant question is also whether the higher risk among those with suboptimal cholesterol lowering was due to their higher cholesterol or whether they have been more stressed than the optimally treated patients because in a recent study by Song et al (3) stress related disorders were strong predictors of CVD. This fact induces yet another bias in the study by Akyea et al. because several studies have shown that stress may raise serum cholesterol substantially (4-7), and stress may increase the risk of CVD in many other ways (8). We consider that mental stress is the most likely explanation of the difference because a recent review of the medical literature has documented that the general view about the role of cholesterol in CVD does not satisfy any of Bradford Hill´s criteria for a medical hypothesis (2).
1. Akyea RK, Kai J, Qureshi N, et al. Heart 2019;0:1–7. doi:10.1136/heartjnl-2018-314253
2. Ravnskov U, de Lorgeril M, Diamond DM, et al. LDL-C does not cause cardiovascular disease: a comprehensive review of current literature. Exp Rev Clin Pharmacol 2018;11:959-70. doi: 10.1080/17512433.2018.1519391.
3. Song H, Fang F, Arnberg FK et al. Stress related disorders and risk of cardiovascular disease: population based, sibling controlled cohort study. BMJ 2019;365:l1255.
4. Friedman M, Rosenman RH, Carroll V. Changes in the serum cholesterol and blood-clotting time in men subjected to cyclic variation of occupational stress. Circulation 1958;17:852-61.
5. Thomas PD, Goodwin JM, Goodwin JS. Effect of social support on stress-related changes in cholesterol level, uric acid level, and immune function in an elderly sample. Am J Psychiatry 1985;142:735-7.
6. Grundy SM, Griffin AC: Effects of periodic mental stress on serum cholesterol levels. Circulation 1959;19:496-8.
7. Muldoon MF, Bachen EA, Manuck SB et al. Acute cholesterol responses to mental stress and change in posture. Arch Intern Med 1992;152:775-80.
8. Thrall G, Lane D, Carroll D, Lip GY. A systematic review of the effects of acute psychological stress and physical activity on haemorheology, coagulation, fibrinolysis and platelet reactivity: Implications for the pathogenesis of acute coronary syndromes. Thromb Res 2007;120:819-47.
Under the "diagnosis" heading the authors asserted that "hypothyroidism can be deemed the aetiology of pericardial effusion or cardiac tamponade if a high TSH level has been found, after excluding other secondary causes like a neoplastic, bacterial or an inflammatory process"(1).. I would add that, if the patient's hypothyroidism is of autoimmune aetiology, Addison's disease is a secondary cause that also requires urgent exclusion(2).
In one report, a 21 year old man presented with cardiac tamponade, in association with a TSH level of 17.9 microUnits/L(normal range 0.35-5.0 microUnits/L), and serum thyroxine and serum tri-iodothyronine levels which were both at the lower limit of the normal range. Serum cortisol, however, was 0.5 micrograms/dl(normal range 3.0-23.0 mcd/dl). Tests for thyroid and adrenal autoantibodies were positive, thereby fulfilling the criteria for Type 2 autoimmune polyglandular syndrome(Type-2 APS).
Comment
On the basis of the above observations the work-up of patients with pericardial effusion of presumed hypothyroid aetiology should include evaluation of adrenal function, because Addison's disease can, in its own right, be the underlying cause of cardiac tamponade(3). Furthermore, irrespective of hormonal status, pericardial effusion in a patient with Type 2 APS may ultimately be attributable to the "serositis" component of that syndrome, rendering the effusion capable of relapsing...
Under the "diagnosis" heading the authors asserted that "hypothyroidism can be deemed the aetiology of pericardial effusion or cardiac tamponade if a high TSH level has been found, after excluding other secondary causes like a neoplastic, bacterial or an inflammatory process"(1).. I would add that, if the patient's hypothyroidism is of autoimmune aetiology, Addison's disease is a secondary cause that also requires urgent exclusion(2).
In one report, a 21 year old man presented with cardiac tamponade, in association with a TSH level of 17.9 microUnits/L(normal range 0.35-5.0 microUnits/L), and serum thyroxine and serum tri-iodothyronine levels which were both at the lower limit of the normal range. Serum cortisol, however, was 0.5 micrograms/dl(normal range 3.0-23.0 mcd/dl). Tests for thyroid and adrenal autoantibodies were positive, thereby fulfilling the criteria for Type 2 autoimmune polyglandular syndrome(Type-2 APS).
Comment
On the basis of the above observations the work-up of patients with pericardial effusion of presumed hypothyroid aetiology should include evaluation of adrenal function, because Addison's disease can, in its own right, be the underlying cause of cardiac tamponade(3). Furthermore, irrespective of hormonal status, pericardial effusion in a patient with Type 2 APS may ultimately be attributable to the "serositis" component of that syndrome, rendering the effusion capable of relapsing or remitting irrespective of concurrent hormone replacement therapy(4).
An important caveat to interpretation of raised TSH levels is that, in the presence of primary hypoadrenalism, a raised serum TSH does not necessarily signify coexistence of primary hypothyroidism. On its own, primary hypoadrenalism can cause elevation of serum TSH which reverts to the normal range during the course of corticosteroid replacement therapy(5). In the latter report a 26 year old man with Addison's disease had a documented pretreatment serum TSH of 32 microUnits/L. Over a 2 year period of corticosteroid replacement therapy his serum TSH progressively fell to 2.5 microUnits/L, without concomitant thyroid replacement therapy. During that period both his serum thyroxine and serum tri-iodothyronine levels remained well within the normal range(5).
Finally, even in the presence of the coexistence of raised serum TSH and subnormal serum thyroxine clinicians should remain vigilant for type 2 APS, notwithstanding the fact that an identical biochemical scenario was depicted by the authors of the clinical vignette(1). In one case report a 24 year old man had a diagnosis of primary hypothyroidism characterised by serum thyroxine 40 nmol/L(normal 60-140 nmol/L), tri-iodothyronine 1.2 nmol/L(normal 1.6-3.0 nmol/L), and serum TSH 90 microUnits/L. However, he deteriorated after commencing thyroid replacement therapy, and this deterioration proved to be attributable to coexisting Addison's disease. Thyroxine was stopped, and he received corticosteroid replacement therapy instead. Over a period of 18 months of corticosteroid replacement therapy he experienced clinical improvement, and his thyroid function tests reverted to the normal range without the benefit of concomitant thyroid replacement therapy(6).
References
(1)Chahine J., Ala CK., Pantalone KM., Klein AL
Pericardial diseases in patients with hypothyroidism
Heart 2019;0:1-7,doi 10.1136/heartjnl-2018-314528
(2) Bacal A., Mathew G., Pyle J., Pauwaa S., Kazi M
Cardiac tamponade as initial presentation of autoimmune ployglandular syndrome type 2
AACE Clinical Case Reports 2018;4:e195-e198
(3) Torfoss D., von der Lippe E., Jacobsen D
Cardiac tamponade preceding adrenal insufficiency-an unusual presentation of Addison's disease: a report of two cases
Journal of Internal Medicine 1997;241:525-528
(4) Tucker WS., Niblack GD., McLean RH., Alspaught MA., Wyatt RJ., Jordan SC et al
Serositis with autoimmune endocrinopathy: Clinical and immunogenetic features
Medicine 1987;66:138-147
(5) Candrina R., Giustina G
Addison's disease and corticosteroid-reversible hypothyroidism
J Endocrinol Invest 1987;10:523-524
(6) Burrows AW
Reversible hypothyroidism after steroid replacement for Addison's disease
Postgrad Med J 1981;57:368-370
We read the article by Godino et al describing the risk of non-revascularisation of a coronary chronic total occlusion (CTO) for the cardiac death, sudden cardiac death and sustained ventricular arrhythmias (SCD/SVA) with great interest 1. After reading in detail, we have the following comments.
At first, although the authors mentioned a little in the DISCUSSION, the effect of medications for the prevention of cardiac death and SCD/SVA may better be clarified in the subjects. As they stated, because those who received CTO lesion revascularisation tend to have longer dual antiplatelet therapy and receive more hospital visit for follow-up coronary angiography to recheck, there might be such confounding factors. For example, the third generation P2Y12 class of adenosine diphosphate (ADP) receptors inhibitor was approved in 2009 in Europe 2. How was its distribution compared to conventional clopidogrel treatment? And appropriate statin treatment would be also associated with plaque stability and reduced cardiac adverse events as well as the beta-blocker administration for the prevention of SCD/SVA 3. Because the follow-up period was long as up to 12-years, the difference of these medication strategies between two groups should be clarified. The same also applies to the used stent types. The importance of current manuscript would be much better after these concerns were clarified.
Second, the multivariate analysis of Table 3 contains 2 factors,...
We read the article by Godino et al describing the risk of non-revascularisation of a coronary chronic total occlusion (CTO) for the cardiac death, sudden cardiac death and sustained ventricular arrhythmias (SCD/SVA) with great interest 1. After reading in detail, we have the following comments.
At first, although the authors mentioned a little in the DISCUSSION, the effect of medications for the prevention of cardiac death and SCD/SVA may better be clarified in the subjects. As they stated, because those who received CTO lesion revascularisation tend to have longer dual antiplatelet therapy and receive more hospital visit for follow-up coronary angiography to recheck, there might be such confounding factors. For example, the third generation P2Y12 class of adenosine diphosphate (ADP) receptors inhibitor was approved in 2009 in Europe 2. How was its distribution compared to conventional clopidogrel treatment? And appropriate statin treatment would be also associated with plaque stability and reduced cardiac adverse events as well as the beta-blocker administration for the prevention of SCD/SVA 3. Because the follow-up period was long as up to 12-years, the difference of these medication strategies between two groups should be clarified. The same also applies to the used stent types. The importance of current manuscript would be much better after these concerns were clarified.
Second, the multivariate analysis of Table 3 contains 2 factors, “CTO not revascularised” and “left ventricular ejection fraction (LVEF)”. However, from Table1, there was significant difference in left ventricular ejection fraction between CTO-R group and CTO-NR group. Thus, I suspect that these 2 factors, “CTO not revascularised” and “LVEF” may have significant multicollinearity. From the METHODS section, the authors wrote that comprehensive set of covariates, based on clinical relevance at univariate analysis and data from previous investigations were used. However, how did you exclude the multicollinearity? If you use the variance inflation factor (VIF), you may better present the VIF of enrolled variables. Because I guess if you include both CTO-NR and LVEF into multivariate analysis, CTO-NR may be excluded and only LVEF was preserved after step-wise method, i.e, the difference of the prognosis may be attributed to only LVEF difference.
Disclosures
The authors have no conflict of interest related to the manuscript.
Acknowledgements
None.
References
1 Godino C, Giannattasio A, Scotti A, et al. Risk of cardiac and sudden death with and without revascularisation of a coronary chronic total occlusion. Heart 2019 Feb 21. pii: heartjnl-2018-314076. doi: 10.1136/heartjnl-2018-314076.
2 Mousa SA, Jeske WP, Fareed J. Antiplatelet therapy prasugrel: a novel platelet ADP P2Y12 receptor antagonist. Clin Appl Thromb Hemost 2010 ;16:170-6.
3 Park JJ, Chae IH, Cho YS, et al. The recanalization of chronic total occlusion leads to lumen area increase in distal reference segments in selected patients: an intravascular ultrasound study. JACC Cardiovasc Interv 2012 ;5:827-36.
Editor, We agree with Lavie et al that the current standard model of delivering cardiac rehabilitation (CR) predominantly in hospital or centre based facilities has reached saturation and we should be looking at offering alternatives which could improve the global suboptimal rates of participation in CR. [1] Uptake of CR in heart failure remains particularly poor with rates of less than 20% in Europe. [2].
Clinicians and commissioners should consider implementing the findings of a UK based multicentre trial on home-based CR [3] which responds to the updated 2018 NICE guidance recommendation that adults with heart failure are offered a “..personalised, exercise-based CR programme – in a format and setting (at home, in the community or in the hospital) that is easily accessible” [https://www.nice.org.uk/guidance/ng106/chapter/Recommendations#cardiac-r... ]
We believe REACH HF to be the largest randomised trial of home based CR (co-developed by clinicians, academics, caregivers and patients) in heart failure with reduced ejection fraction and it provides important new evidence for a novel home-based CR programme in terms of benefit to patients and their caregivers. [3]
The results of the REACH HF trial show that it is possible to significantly improve patients’ health related quality of life and that the intervention has a cost of £418 per patient, within th...
Editor, We agree with Lavie et al that the current standard model of delivering cardiac rehabilitation (CR) predominantly in hospital or centre based facilities has reached saturation and we should be looking at offering alternatives which could improve the global suboptimal rates of participation in CR. [1] Uptake of CR in heart failure remains particularly poor with rates of less than 20% in Europe. [2].
Clinicians and commissioners should consider implementing the findings of a UK based multicentre trial on home-based CR [3] which responds to the updated 2018 NICE guidance recommendation that adults with heart failure are offered a “..personalised, exercise-based CR programme – in a format and setting (at home, in the community or in the hospital) that is easily accessible” [https://www.nice.org.uk/guidance/ng106/chapter/Recommendations#cardiac-r... ]
We believe REACH HF to be the largest randomised trial of home based CR (co-developed by clinicians, academics, caregivers and patients) in heart failure with reduced ejection fraction and it provides important new evidence for a novel home-based CR programme in terms of benefit to patients and their caregivers. [3]
The results of the REACH HF trial show that it is possible to significantly improve patients’ health related quality of life and that the intervention has a cost of £418 per patient, within the current NHS tariff of £477 for CR. [3]
Importantly, we have recently also demonstrated the long term cost effectiveness of home-based CR programmes like REACH HF in a cost effectiveness modelling analysis [4].This analysis shows that REACH-HF has an average cost per quality adjusted life year gained (QALY) of £1,720 with a 78% probability of being cost effective at the UK accepted threshold of £20,000/QALY gained. [4]
Home based CR programmes allow the delivery of care closer to where people need it and could also help towards achieving the ambitious target of offering CR to 85% of eligible patients set in the recently released NHS long-term plan (https://www.longtermplan.nhs.uk/online-version/chapter-3-further-progres...)
We believe that programmes, such as REACH-HF, can provide an affordable, cost effective CR intervention for service commissioners which can offset the current inequity in access to rehabilitation by patients with heart failure both in the UK and elsewhere.
Authors: Hasnain M Dalal (a, b), Rod S Taylor (a, c), Colin Greaves (d) and Patrick Doherty (e)
Affiliations:(a) Institute of Health Research, University of Exeter Medical School, Exeter, UK (b) Royal Cornwall Hospitals NHS Trust, Truro, UK (c) Institute of Health and Well Being, School of Medicine, Dentistry & Nursing, University of Glasgow, Glasgow and Institute of Health Research, University of Exeter Medical School, Exeter UK (d) School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Edgbaston, UK (e) Department of Health Sciences, University of York, York, UK
References
1. Lavie CJ, Kachur S and Milani R V. Making cardiac rehabilitation more available and affordable. Heart 2019; 105: 94–95. doi:10.1136/heartjnl-2018-313762
2. Bjarnason-Wehrens B, McGee H, Zwisler AD, Piepoli M, et al. Cardiac rehabilitation in Europe: results from the European Cardiac Rehabilitation Inventory Survey. Eur J Cardiovasc Prev Rehabil 2010;17:410-8. doi.org/10.1097/HJR.0b013e328334f42
3. Dalal HM, Taylor RS, Jolly K, et al. The effects and costs of home-based rehabilitation for heart failure with reduced ejection fraction: The REACH-HF multicentre randomized controlled trial. Eur J Prev Cardiol, Epub ahead of print 10 October 2018. doi.org/ 10.1177/2047487318806358.
4. Taylor RS, Sadler S, Dalal HM et al "The cost effectiveness of REACH-HF and home-based cardiac rehabilitation in the treatment of heart failure with reduced ejection fraction: a decision model-based analysis" Eur J Prev Cardiol, 2019 10.1177/2047487319833507 [In press, accepted 5.2.2019]
Given the fact that the entire purpose of blood pressure measurement is to identify the cut-off level of blood pressure that increases the risk for cerebral, cardiac, and renal events, and that "brachial blood pressure can be an imperfect surrogate for central aortic pressure"(1), the latter being independently correlated with incident cardiovascular disease and cardiovascular risk(2), the ultimate test of the utility of the novel cuffless device is the degree to which it deviates from central blood pressure. Only 33% of conventional brachial blood pressure values have been found to lie within 5 mm Hg below or above intra-arterial values(3). The other challenge is the validity of cuffless blood pressure measurements obtained from patients with atrial fibrillation
References
(1)Messerli F., Williams B., Ritz E
Essential hypertension
Lancet 2007;370:591-603
(2) Agabiti-Rosei E., Mancia G., O'Rourke MF et al
Cntral blood pressure measurements and antihypertensive therapy: A consensus statement
Hypertension 2007;50:154-160
(3)Manios E., Vemmos K., Tsivgoulis G et al
Comparison of noninvasive oscillometric and intraarterial blood pressure measurements in hyperacute stroke
Blood Press Monit 2007;12:149-156
Gardezi and colleagues (1) report on the limited accuracy for detection of valvular heart disease (VHD) by cardiac auscultation in asymptomatic patients in primary care. VHD was categorized as either mild or significant and cardiac auscultation was dichotomized in either a present or absent murmur. The authors propose a low sensitivity and modest specificity of cardiac auscultation by general practitioners and by cardiologists to assess VHD.
However, the authors underestimated the specificity and positive predictive value of cardiac auscultation for the assessment of VHD. Patients with a cardiac murmur in whom, by transthoracic echocardiography, mild VHD was detected were included in the ‘negative’ group for assessing significant VHD and more importantly, vice versa. By doing so, many murmurs are classified as false-positive although VHD was present, either mild or significant. We believe that the “true negative” group only includes those patients without any VHD on echocardiography. This would increase the specificity of cardiac auscultation by general practitioners from 67% to 76% and from 81% to 93% for cardiologists, which results in much higher positive predictive values for significant VHD. While it does not change the reported low sensitivity of cardiac auscultation, which remains rather unsatisfactory, this perspective would make the conclusions of this paper at least a little less detrimental to the good old stethoscope.
Gardezi and colleagues (1) report on the limited accuracy for detection of valvular heart disease (VHD) by cardiac auscultation in asymptomatic patients in primary care. VHD was categorized as either mild or significant and cardiac auscultation was dichotomized in either a present or absent murmur. The authors propose a low sensitivity and modest specificity of cardiac auscultation by general practitioners and by cardiologists to assess VHD.
However, the authors underestimated the specificity and positive predictive value of cardiac auscultation for the assessment of VHD. Patients with a cardiac murmur in whom, by transthoracic echocardiography, mild VHD was detected were included in the ‘negative’ group for assessing significant VHD and more importantly, vice versa. By doing so, many murmurs are classified as false-positive although VHD was present, either mild or significant. We believe that the “true negative” group only includes those patients without any VHD on echocardiography. This would increase the specificity of cardiac auscultation by general practitioners from 67% to 76% and from 81% to 93% for cardiologists, which results in much higher positive predictive values for significant VHD. While it does not change the reported low sensitivity of cardiac auscultation, which remains rather unsatisfactory, this perspective would make the conclusions of this paper at least a little less detrimental to the good old stethoscope.
References
1. Gardezi SKM, Myerson SG, Chambers J, Coffey S, d'Arcy J, Hobbs FDR, et al. Cardiac auscultation poorly predicts the presence of valvular heart disease in asymptomatic primary care patients. Heart. 2018;104(22):1832-5.
An imprtant caveat to reliance on brain natriuretic peptide(BNP) levels > 100 pg/ml to trigger referral to secondary care(1) is that there exists a clinical phenotype of congestive heart failure(CHF) characterised by BNP equal to or less than 100 pg/ml(2).. In the latter study 46 out of 1159 subjects with CHF and left ventricular ejection fraction(LVEF) > 50%, 46 subjects were characterised by BNP equal to or less than 100 pg/ml. Heart failure symptoms such as effort dyspnoea were equally prevalent(93% vs 90%) in subject with BNP equal to or less than 100 pg/ml vs counterparts with BNP > 100 pg/ml(2). The same was true of orthopnoea(48% vs 48%) and paroxysmal nocturanal dyspnoea(28% vs 29%)(2).
The other caveat is that constrictive pericarditis(CP), an entity characterised by symptoms such as effort dyspnoea and pedal oedema, similar to those in CHF, may be characterised by BNP as low as 50 pg/ml and 88 pg/ml, respectively, in spite of coexistence of New York Heart Association functional class III and IV symptoms(3), and natriuretic propeptide tyype B 147 pg/ml in spite of worsening dyspnoea(4). An overriding consideration is the "diagnostic value of physical examination....in primary care"(5) which includes evaluation of jugular venous pressure(JVP)(5). In the latter study elevation of JVP contributed 12 points towards a score of >54 needed to generate a >70% probability of CHF(5). In CP marked elevation of JVP is almost universal(6)....
An imprtant caveat to reliance on brain natriuretic peptide(BNP) levels > 100 pg/ml to trigger referral to secondary care(1) is that there exists a clinical phenotype of congestive heart failure(CHF) characterised by BNP equal to or less than 100 pg/ml(2).. In the latter study 46 out of 1159 subjects with CHF and left ventricular ejection fraction(LVEF) > 50%, 46 subjects were characterised by BNP equal to or less than 100 pg/ml. Heart failure symptoms such as effort dyspnoea were equally prevalent(93% vs 90%) in subject with BNP equal to or less than 100 pg/ml vs counterparts with BNP > 100 pg/ml(2). The same was true of orthopnoea(48% vs 48%) and paroxysmal nocturanal dyspnoea(28% vs 29%)(2).
The other caveat is that constrictive pericarditis(CP), an entity characterised by symptoms such as effort dyspnoea and pedal oedema, similar to those in CHF, may be characterised by BNP as low as 50 pg/ml and 88 pg/ml, respectively, in spite of coexistence of New York Heart Association functional class III and IV symptoms(3), and natriuretic propeptide tyype B 147 pg/ml in spite of worsening dyspnoea(4). An overriding consideration is the "diagnostic value of physical examination....in primary care"(5) which includes evaluation of jugular venous pressure(JVP)(5). In the latter study elevation of JVP contributed 12 points towards a score of >54 needed to generate a >70% probability of CHF(5). In CP marked elevation of JVP is almost universal(6). In a simplified procedure for evaluation of JVP, where this parameter was evaluated with the patient sitting bolt upright, a deep venous column visibly distended above the right clavicle had a sensitivity of 65% and a specificity of 85% to identify truly elevated venous pressure, where the "gold standard" was elevation of right atrial pressure(evaluated by catheterisation)(7). Missed diagnosis of CP is highly prevalent even in the UK(8), notwithstanding the fact that CP is a curable cause of CHF(9), characterised by LVEF > 50% in the majority of cases, and by LVEF < 40% in 20.9% of 43 subjects in one study(10). In the UK the index of suspicion for CP should be raised by a history of previous cardiac surgery(11) or radiation treatment(12).
References
(1) Hayhoe B., Kim D., Aykin P., Majeed FA., Cowie MR., Bottle A
Adherence to guidelines in management of symptoms suggestive of heart failure in primary care
Heart 2018 E pub ahead of print
(2) Anjan VY., Loftus TM., Burke MA., Akhter N., Fonarow GC., Gheorghiade M., Shah SF
Prevalence clinical phenotype and outcomes associated with normal B-type ntriuretic peptide levels in heart failure with preserved ejection fraction
Am J Cardiol 2012;110:870-876
(3) Leya FS., Arab D., Joyal D., Shioura KM., Lewis BE., Steen LH., Cho L
The efficacy of brain natriuretic peptide levels in differentiating constrictive pericarditis from restrictive cardiomyopathy
JACC 2005;45:1900-1902
(4)Grabysa R., Widawski T., Przelaskowski P
Don't blindly trust in BNP concentration: A case of constrictive pericarditis
Int J Cardiol 2015;180:50-51
(5)Kelder JC., Cramer MJ., van Wijngaarden J., van Tooren R., Mosterd A., Moons KG., Lammers JW et al
The diagnostic value of physical examination and additional testing in primary care patients with suspected heart failure
Circulation 2011;124:2865-2873
(6) Gimlette TMD
Constrictive pericarditis
Brit Heart J 1959;21;9-16
(7)Sinisalo J., Rapola JP., Rossinen J., Kupari M
Simplifying the estimation of jugular venous pressureAm J cardiol 2007;100;1779-1781
(8) Marshall A., Ring N., Lewis T
Constrictive pericarditis lessons from the past five years' experience in the South West Cardiothoracic Centre
ckinical Medicine 2006;6:592-597
(9) Syed FF., Schaff HV., Oh JK
Constricitve pericarditis a curable diastolic failure
Nature Reviews Cardiology 2014;11:530-544
(10) Oreto L., Mayer A., Todaro MC., Mori N., Kress DC., Kleinman LH., Allaqaband S et al
Contemporary clinical spectrum of constricitive pericarditis : a 10 year experience
Int J Cardiol 2013;163:339-341
(11) Gaudino M., Anselmi A., Pavone N., Massetti M
Constrictive pericarditis after cardiac surgery AnnThorac Surg 2013;95;731-736
(12) Szabo G., Schmack B., Bulul C., Soos P., Weymann A., Stadfeld S., Karck M
Constrictive pericarditis risks aetiologies and aoutcomes after total pericardiectomy: 24 years of experience
Europenn Journal of cradiothoracic surgery 2013;44:1023-1028
To the Editor,
We read with interest the paper by Ikenaga et al. (1), who must be commended for their detailed report on the determinants of persistent iatrogenic atrial septal defect (iASD) following percutaneous mitral valve clip (MV clip) placement. The authors found that elevated left atrial (LA) pressure after the MV clip procedure was the main determinant of persistent iASD during follow-up. Remarkably, in spite of their poorer clinical condition, patients with and without persistent iASD had similar outcomes during follow-up. This suggested that interatrial shunt has a benefit in some MV clip patients. Previous studies that evaluated the usefulness of an interatrial shunt device for treating heart failure patients without valve disease also showed a significant benefit of the shunt in patients with high LA pressure (2, 3).
However, these findings disagree with other findings of the persistence of iASD after MV clip placement with negative outcomes, mainly due to right ventricle (RV) claudication (4). Indeed, previous studies of the interatrial shunt device suggest that the size of the shunt plays a key role in outcomes. Indeed, the ideal shunt size should allow the reduction of LA pressure without hampering right heart function. The maximum interatrial shunt devices are 5 mm2 (3); too large iASDs may increase the Qp/Qs enough to cause RV failure, while too small iASDs may be have negligible hemodynamical and clinical results. No MV clip studies reported...
To the Editor,
We read with interest the paper by Ikenaga et al. (1), who must be commended for their detailed report on the determinants of persistent iatrogenic atrial septal defect (iASD) following percutaneous mitral valve clip (MV clip) placement. The authors found that elevated left atrial (LA) pressure after the MV clip procedure was the main determinant of persistent iASD during follow-up. Remarkably, in spite of their poorer clinical condition, patients with and without persistent iASD had similar outcomes during follow-up. This suggested that interatrial shunt has a benefit in some MV clip patients. Previous studies that evaluated the usefulness of an interatrial shunt device for treating heart failure patients without valve disease also showed a significant benefit of the shunt in patients with high LA pressure (2, 3).
However, these findings disagree with other findings of the persistence of iASD after MV clip placement with negative outcomes, mainly due to right ventricle (RV) claudication (4). Indeed, previous studies of the interatrial shunt device suggest that the size of the shunt plays a key role in outcomes. Indeed, the ideal shunt size should allow the reduction of LA pressure without hampering right heart function. The maximum interatrial shunt devices are 5 mm2 (3); too large iASDs may increase the Qp/Qs enough to cause RV failure, while too small iASDs may be have negligible hemodynamical and clinical results. No MV clip studies reported iASD size, which can easily be estimated by Doppler. Thus, sizing the residual iASD may be appropriate following a MV clip procedure. Furthermore, MV disease is often associated with significant pulmonary hypertension and with right heart damage (i.e. tricuspid regurgitation). Thus, even a small interatrial shunt may be deleterious, causing progressive right heart overload and dysfunction. This is the likely scenario in a significant number of MV clip patients (2,3).
Ongoing phase 3 randomized clinical trials in heart failure should provide further insights into the effects of an interatrial shunt. REDUCE LAP-HF II (NCT03088033) is a randomized controlled trial comparing the clinical efficacy of an interatrial shunt device versus optimal medical treatment in symptomatic patients with left ventricular ejection fraction (LVEF) >40%. REDUCE LAP HF-III (NCT03191656) is recruiting patients with preserved or mildly reduced LVEF to determine the benefits (functional status, quality of life) of this therapy at a 12-month follow-up. RELIEVE-HF (NCT03499236) is a randomized controlled trial comparing the second generation (valveless) V-Wave device with optimal medical therapy in patients with preserved or reduced LVEF.
REFERENCES
1 Ikenaga H, Hayashi A, Nagaura T, Yamaguchi S, Yoshida J, Rader F, Siegel RJ, Kar S, Shiota T. Left atrial pressure is associated with iatrogenic atrial septal defect after mitral valve clip. Heart. 2018. pii: heartjnl-2018-313839. doi: 10.1136/heartjnl-2018-313839. [Epub ahead of print]
2 Rodés-Cabau J, Bernier M, Amat-Santos IJ, Ben Gal T, Nombela-Franco L, García Del Blanco B, Kerner A, Bergeron S, Del Trigo M, Pibarot P, Shkurovich S, Eigler N, Abraham WT. Interatrial shunting for heart failure: early and late results from the first-in-human experience with the v-wave system. JACC Cardiovasc Interv. 2018 Nov 26;11(22):2300–10.
3 Del Trigo M, Bergeron S, Bernier M, Amat-Santos IJ, Puri R, Campelo-Parada F, Altisent OA, Regueiro A, Eigler N, Rozenfeld E, Pibarot P, Abraham WT, Rodés-Cabau J. Unidirectional left-to-right interatrial shunting for treatment of patients with heart failure with reduced ejection fraction: a safety and proof-of-principle cohort study. Lancet. 2016 Mar 26;387(10025):1290–7.
4 Schueler R, Öztürk C, Wedekind JA, Werner N, Stöckigt F, Mellert F, Nickenig G, Hammerstingl C. Persistence of iatrogenic atrial septal defect after interventional mitral valve repair with the MitraClip system: a note of caution. JACC Cardiovasc Interv. 2015 Mar;8(3):450–9.
This study has already been inappropriately quoted in the media which is what the public read and misinformation is propagating. The authors need to take some responsibility for failing to point out that the dosing of the statins prescribed (most likely archaic low dose simvastatin) isn't analysed and long term compliance isn't addressed in this ' primary prevention population based longitudinal non interventional study'
Show MoreCardiologists are going to inundated with questions from patients with coronary disease on statins who have misinterpreted information which is incomplete and misrepresented - the title of the study needs to be highlighted 'Initiation of statins' is well put and needs to be remembered. The study cannot address the 'ongoing management' of cardiovascular risk with appropriate cardiovascular investigation of patients and optimization of preventative strategies as this study does not address this crucial aspect.
It is already well proven that only moderate to high dose statin therapy has a proven biological anti-atherogenic effect so that low doses initiated in general practice are actually ineffective and this is what the study shows NOT that statins are ineffective but that medical practice of blanket prescribing of low doses of statins is ineffective without monitoring of response and ongoing titration to achieve evidence based targets. This omission from the conclusions needs to be corrected and it ne...
The conclusion of this article was twofold: 1) approximately half of primary care patients put on statins did not achieve at least a 40% reduction in LDL-Cholesterol (the sub-optimal group) and 2) those who did (the optimal group) had fewer cardiovascular incidents over the next (approximately six) years.
Table 1 in the paper shows that the sub-optimal group have 1.43 times the “alcohol misuse” of the optimal group. There is no more information on alcohol consumption beyond this. Were the alcohol misusers also far less likely to be non or moderate drinkers and far more likely to be heavy and frequent drinkers?
The smoking information shows that, from the limited information available, the sub-optimal group were 25% more likely to be smokers. However, there is no smoking information for 96% of patients. There is no activity information – were the drinking/smokers more likely to be sedentary? Were they more likely to be obese?
There were more men in the sub-optimal group. The sub-optimal patients were more likely to be poorly-controlled diabetics and less likely to have hypertension treated.
Correspondence with the researchers confirmed that the HRs in Table 2 were not adjusted for anything other than age and baseline LDL-Cholesterol. They were not adjusted for alcohol misuse, or smoking, or gender, or any other lifestyle factors that were known to be different between the two groups – even with vast amounts of missing information.
The enti...
Show MoreIn their prospective cohort study of 165,411 primary care patients, Akyea et al. claim that suboptimal responders on statin treatment will experience significantly increased risk of future cardiovascular disease (CVD)(1). As many cardiovascular events may heal without serious health problems, we consider mortality as the most important outcome. Among the 80,802 patients with optimal cholesterol lowering, 821 (1.01 %) died from CVD. Among the 84,609 patients with suboptimal cholesterol-lowering 873 (1.03 %) died. This means that to prevent one cardiovascular death by optimal cholesterol lowering you have to increase the degree of lowering in 5,000 patients for six years. This is hardly a benefit because several independent researchers have reported that serious side effects from statin treatment are much more common than reported in the statin trials (2). The small numbers reported in the trial reports are achieved by excluding participants who suffer from side effects of the drug during a few weeks long run-in period before the start of the trial. That this is an effective method to lower the number of side effects appeared in the IDEAL trial where this method wasn´t used and where a high statin dose was compared with a low dose, because in that trial almost half of the participants in both groups suffered from serious side effects (2).
Furthermore, Akyea et al. have not reported total mortality in the two groups. This failure may introduce another bias because tota...
Show MoreUnder the "diagnosis" heading the authors asserted that "hypothyroidism can be deemed the aetiology of pericardial effusion or cardiac tamponade if a high TSH level has been found, after excluding other secondary causes like a neoplastic, bacterial or an inflammatory process"(1).. I would add that, if the patient's hypothyroidism is of autoimmune aetiology, Addison's disease is a secondary cause that also requires urgent exclusion(2).
Show MoreIn one report, a 21 year old man presented with cardiac tamponade, in association with a TSH level of 17.9 microUnits/L(normal range 0.35-5.0 microUnits/L), and serum thyroxine and serum tri-iodothyronine levels which were both at the lower limit of the normal range. Serum cortisol, however, was 0.5 micrograms/dl(normal range 3.0-23.0 mcd/dl). Tests for thyroid and adrenal autoantibodies were positive, thereby fulfilling the criteria for Type 2 autoimmune polyglandular syndrome(Type-2 APS).
Comment
On the basis of the above observations the work-up of patients with pericardial effusion of presumed hypothyroid aetiology should include evaluation of adrenal function, because Addison's disease can, in its own right, be the underlying cause of cardiac tamponade(3). Furthermore, irrespective of hormonal status, pericardial effusion in a patient with Type 2 APS may ultimately be attributable to the "serositis" component of that syndrome, rendering the effusion capable of relapsing...
To the Editor
We read the article by Godino et al describing the risk of non-revascularisation of a coronary chronic total occlusion (CTO) for the cardiac death, sudden cardiac death and sustained ventricular arrhythmias (SCD/SVA) with great interest 1. After reading in detail, we have the following comments.
Show MoreAt first, although the authors mentioned a little in the DISCUSSION, the effect of medications for the prevention of cardiac death and SCD/SVA may better be clarified in the subjects. As they stated, because those who received CTO lesion revascularisation tend to have longer dual antiplatelet therapy and receive more hospital visit for follow-up coronary angiography to recheck, there might be such confounding factors. For example, the third generation P2Y12 class of adenosine diphosphate (ADP) receptors inhibitor was approved in 2009 in Europe 2. How was its distribution compared to conventional clopidogrel treatment? And appropriate statin treatment would be also associated with plaque stability and reduced cardiac adverse events as well as the beta-blocker administration for the prevention of SCD/SVA 3. Because the follow-up period was long as up to 12-years, the difference of these medication strategies between two groups should be clarified. The same also applies to the used stent types. The importance of current manuscript would be much better after these concerns were clarified.
Second, the multivariate analysis of Table 3 contains 2 factors,...
Editor, We agree with Lavie et al that the current standard model of delivering cardiac rehabilitation (CR) predominantly in hospital or centre based facilities has reached saturation and we should be looking at offering alternatives which could improve the global suboptimal rates of participation in CR. [1] Uptake of CR in heart failure remains particularly poor with rates of less than 20% in Europe. [2].
Show MoreClinicians and commissioners should consider implementing the findings of a UK based multicentre trial on home-based CR [3] which responds to the updated 2018 NICE guidance recommendation that adults with heart failure are offered a “..personalised, exercise-based CR programme – in a format and setting (at home, in the community or in the hospital) that is easily accessible” [https://www.nice.org.uk/guidance/ng106/chapter/Recommendations#cardiac-r... ]
We believe REACH HF to be the largest randomised trial of home based CR (co-developed by clinicians, academics, caregivers and patients) in heart failure with reduced ejection fraction and it provides important new evidence for a novel home-based CR programme in terms of benefit to patients and their caregivers. [3]
The results of the REACH HF trial show that it is possible to significantly improve patients’ health related quality of life and that the intervention has a cost of £418 per patient, within th...
Given the fact that the entire purpose of blood pressure measurement is to identify the cut-off level of blood pressure that increases the risk for cerebral, cardiac, and renal events, and that "brachial blood pressure can be an imperfect surrogate for central aortic pressure"(1), the latter being independently correlated with incident cardiovascular disease and cardiovascular risk(2), the ultimate test of the utility of the novel cuffless device is the degree to which it deviates from central blood pressure. Only 33% of conventional brachial blood pressure values have been found to lie within 5 mm Hg below or above intra-arterial values(3). The other challenge is the validity of cuffless blood pressure measurements obtained from patients with atrial fibrillation
References
(1)Messerli F., Williams B., Ritz E
Essential hypertension
Lancet 2007;370:591-603
(2) Agabiti-Rosei E., Mancia G., O'Rourke MF et al
Cntral blood pressure measurements and antihypertensive therapy: A consensus statement
Hypertension 2007;50:154-160
(3)Manios E., Vemmos K., Tsivgoulis G et al
Comparison of noninvasive oscillometric and intraarterial blood pressure measurements in hyperacute stroke
Blood Press Monit 2007;12:149-156
Gardezi and colleagues (1) report on the limited accuracy for detection of valvular heart disease (VHD) by cardiac auscultation in asymptomatic patients in primary care. VHD was categorized as either mild or significant and cardiac auscultation was dichotomized in either a present or absent murmur. The authors propose a low sensitivity and modest specificity of cardiac auscultation by general practitioners and by cardiologists to assess VHD.
However, the authors underestimated the specificity and positive predictive value of cardiac auscultation for the assessment of VHD. Patients with a cardiac murmur in whom, by transthoracic echocardiography, mild VHD was detected were included in the ‘negative’ group for assessing significant VHD and more importantly, vice versa. By doing so, many murmurs are classified as false-positive although VHD was present, either mild or significant. We believe that the “true negative” group only includes those patients without any VHD on echocardiography. This would increase the specificity of cardiac auscultation by general practitioners from 67% to 76% and from 81% to 93% for cardiologists, which results in much higher positive predictive values for significant VHD. While it does not change the reported low sensitivity of cardiac auscultation, which remains rather unsatisfactory, this perspective would make the conclusions of this paper at least a little less detrimental to the good old stethoscope.
References
Show More1. Gardezi S...
An imprtant caveat to reliance on brain natriuretic peptide(BNP) levels > 100 pg/ml to trigger referral to secondary care(1) is that there exists a clinical phenotype of congestive heart failure(CHF) characterised by BNP equal to or less than 100 pg/ml(2).. In the latter study 46 out of 1159 subjects with CHF and left ventricular ejection fraction(LVEF) > 50%, 46 subjects were characterised by BNP equal to or less than 100 pg/ml. Heart failure symptoms such as effort dyspnoea were equally prevalent(93% vs 90%) in subject with BNP equal to or less than 100 pg/ml vs counterparts with BNP > 100 pg/ml(2). The same was true of orthopnoea(48% vs 48%) and paroxysmal nocturanal dyspnoea(28% vs 29%)(2).
Show MoreThe other caveat is that constrictive pericarditis(CP), an entity characterised by symptoms such as effort dyspnoea and pedal oedema, similar to those in CHF, may be characterised by BNP as low as 50 pg/ml and 88 pg/ml, respectively, in spite of coexistence of New York Heart Association functional class III and IV symptoms(3), and natriuretic propeptide tyype B 147 pg/ml in spite of worsening dyspnoea(4). An overriding consideration is the "diagnostic value of physical examination....in primary care"(5) which includes evaluation of jugular venous pressure(JVP)(5). In the latter study elevation of JVP contributed 12 points towards a score of >54 needed to generate a >70% probability of CHF(5). In CP marked elevation of JVP is almost universal(6)....
To the Editor,
Show MoreWe read with interest the paper by Ikenaga et al. (1), who must be commended for their detailed report on the determinants of persistent iatrogenic atrial septal defect (iASD) following percutaneous mitral valve clip (MV clip) placement. The authors found that elevated left atrial (LA) pressure after the MV clip procedure was the main determinant of persistent iASD during follow-up. Remarkably, in spite of their poorer clinical condition, patients with and without persistent iASD had similar outcomes during follow-up. This suggested that interatrial shunt has a benefit in some MV clip patients. Previous studies that evaluated the usefulness of an interatrial shunt device for treating heart failure patients without valve disease also showed a significant benefit of the shunt in patients with high LA pressure (2, 3).
However, these findings disagree with other findings of the persistence of iASD after MV clip placement with negative outcomes, mainly due to right ventricle (RV) claudication (4). Indeed, previous studies of the interatrial shunt device suggest that the size of the shunt plays a key role in outcomes. Indeed, the ideal shunt size should allow the reduction of LA pressure without hampering right heart function. The maximum interatrial shunt devices are 5 mm2 (3); too large iASDs may increase the Qp/Qs enough to cause RV failure, while too small iASDs may be have negligible hemodynamical and clinical results. No MV clip studies reported...
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