The authors thank Siniorakis et al. for highlighting the cardioprotective effect of enkephalins (ENK) as well as their potential role as biomarkers in post infarct heart failure (HF).[1] We had restricted our discussion around ENK and other vasoactive peptides to allow for a broader analysis of various concepts and also to comply with article length limitations. We note that the comments of Siniorakis et al. are consistent with the objective of our article, which is to highlight the potential role of other vasoactive pathways beyond that of the natriuretic peptide system when using sacubitril / valsartan in HF.[2] Indeed there is evidence to suggest that proenkephalin may be a prognostic indicator in acute heart failure.[3]
References:
1 Siniorakis E, Arapi S, Kaplanis I, et al. Cardioprotective effects of enkephalins and potential interference from neprilysin inhibitors. [Letter to Editor], Heart 2017.
2 Singh JSS, Burrell LM, Cherif M, et al. Sacubitril/valsartan: beyond natriuretic peptides. Heart 2017.
3 Ng LL, Squire IB, Jones DJ, et al. Proenkephalin, Renal Dysfunction, and Prognosis in Patients With Acute Heart Failure: A GREAT Network Study. J Am Coll Cardiol 2017;69:56-69.
We read with great interest the recent article by Bulluck and colleagues regarding use of preoperative serum neutrophil gelatinase-associated lipocalin (sNGAL) to predict acute kidney injury (AKI) during hospitalisation and 1-year cardiovascular and all-cause mortality following adult cardiac surgery. They showed that preoperative sNGAL was an independent predictor of postoperative AKI and 1-year mortality. Although the valuable study has been actualized, two issues in methodology seem important to avoid any optimistic interpretation or misinterpretation of results.
First, when using the KDIGO criteria to define and grade AKI, Bulluck et al1 used a time window of 72 h to include patients with different serum creatinine (sCr) increases from baseline, rather than 48 h, as specified by the guideline. Furthermore, it was unclear whether the sCr levels used for diagnosis and staging of AKI had been corrected based on perioperative fluid balance. The available evidence shows that not adjusting sCr levels for fluid balance may underestimate incidence of AKI after cardiac surgery, as a positive perioperative fluid balance may dilute sCr.2
Second, this study only assessed the associations of preoperative sNGAL levels with the risks of postoperative AKI and 1-year mortality, but did not provide the true predictive performances of preoperative sNGAL. To determine discriminative ability of preoperative sNGAL for adverse postoperative outcomes, the receiver operating charac...
We read with great interest the recent article by Bulluck and colleagues regarding use of preoperative serum neutrophil gelatinase-associated lipocalin (sNGAL) to predict acute kidney injury (AKI) during hospitalisation and 1-year cardiovascular and all-cause mortality following adult cardiac surgery. They showed that preoperative sNGAL was an independent predictor of postoperative AKI and 1-year mortality. Although the valuable study has been actualized, two issues in methodology seem important to avoid any optimistic interpretation or misinterpretation of results.
First, when using the KDIGO criteria to define and grade AKI, Bulluck et al1 used a time window of 72 h to include patients with different serum creatinine (sCr) increases from baseline, rather than 48 h, as specified by the guideline. Furthermore, it was unclear whether the sCr levels used for diagnosis and staging of AKI had been corrected based on perioperative fluid balance. The available evidence shows that not adjusting sCr levels for fluid balance may underestimate incidence of AKI after cardiac surgery, as a positive perioperative fluid balance may dilute sCr.2
Second, this study only assessed the associations of preoperative sNGAL levels with the risks of postoperative AKI and 1-year mortality, but did not provide the true predictive performances of preoperative sNGAL. To determine discriminative ability of preoperative sNGAL for adverse postoperative outcomes, the receiver operating characteristic curve analysis should be performed to provide the optimal cutoff values of preoperative sNGAL for postoperative AKI and mortality as well as its sensitivity, specificity, and positive and negative predictive values. The optimal cutoff value is the one that has the highest sensitivity and specificity combined. By providing the predicted probabilities and observed frequencies for postoperative AKI and mortality based on the cutoff values of preoperative sNGAL, the readers can estimate whether there is a good overall agreement between predicted probabilities and observed frequencies in the development and the validation sets. This study identified preoperative sNGAL as a predictor of AKI, but c-statistic was only improved to 0.69 when controlling perioperative risk factors affecting postoperative myocardial and kidney injuries. Traditionally, a c-statistic of 0.5 means random occurrence, whereas a c-statistic > 0.7 signifies adequate discrimination and > 0.8 indicates strong discrimination.
REFERENCES
1 Bulluck H, Maiti R, Chakraborty B, et al. Neutrophil gelatinase-associated lipocalin prior to cardiac surgery predicts acute kidney injury and mortality. Heart 2017 Aug 9. DOI: 10.1136/heartjnl-2017-311760.
2 Moore E, Tobin A, Reid D, et al. The impact of fluid balance on the detection, classification and outcome of acute kidney injury after cardiac surgery. J Cardiothorac Vasc Anesth 2015; 29:1229-35.
3 Merkow RP, Hall BL, Cohen ME, et al. Relevance of the c-statistic when evaluating risk-adjustment models in surgery. J Am Coll Surg 2012; 214:822-30.
To the Editor, Singh et al¹ refer to cardiocirculatory effects of sacubitril/valsartan beyond those related to the activation of the natriuretic peptide system. Sacubitril, by inhibiting neprilysin (NEP), upregulates various vasoactive peptides, with enkephalins (ENK) performing a major role among them. It is not by chance that PARADIGM-HF trial, which established the novel NEP inhibitor, bestows NEP with the name ‘enkephalinase’, since the latter catalyzes the degradation of ENK. Singh et al¹ concentrate on the sacubitril-related augmentation of substance P, bradykinin and adrenomedullin, while they refrain from referring to ENK. ENK and proenkephalins, their precursors, are endogenous opioids, ligands to delta and kappa opioid receptors (ORs), which are abundant in the neural system as well as in the myocardium. The endogenous opioid system exerts a significant antinociceptive action in the heart, as we deduce by observations in animal and human models². An important field where ENK have already demonstrated their cardioprotective role, is reperfusion-related ischemia, with myocardial infarction, coronary artery by pass and angioplasty constituting the principal clinical equivalents in this setting³. In all the above mentioned conditions, ENK are overexpressed, both in the neural system and locally in the myocardium. ENK action during reperfusion ischaemia is exerted via various pathways. In detail, they increase intracellular Ca²+ levels, while, simultaneously, they ope...
To the Editor, Singh et al¹ refer to cardiocirculatory effects of sacubitril/valsartan beyond those related to the activation of the natriuretic peptide system. Sacubitril, by inhibiting neprilysin (NEP), upregulates various vasoactive peptides, with enkephalins (ENK) performing a major role among them. It is not by chance that PARADIGM-HF trial, which established the novel NEP inhibitor, bestows NEP with the name ‘enkephalinase’, since the latter catalyzes the degradation of ENK. Singh et al¹ concentrate on the sacubitril-related augmentation of substance P, bradykinin and adrenomedullin, while they refrain from referring to ENK. ENK and proenkephalins, their precursors, are endogenous opioids, ligands to delta and kappa opioid receptors (ORs), which are abundant in the neural system as well as in the myocardium. The endogenous opioid system exerts a significant antinociceptive action in the heart, as we deduce by observations in animal and human models². An important field where ENK have already demonstrated their cardioprotective role, is reperfusion-related ischemia, with myocardial infarction, coronary artery by pass and angioplasty constituting the principal clinical equivalents in this setting³. In all the above mentioned conditions, ENK are overexpressed, both in the neural system and locally in the myocardium. ENK action during reperfusion ischaemia is exerted via various pathways. In detail, they increase intracellular Ca²+ levels, while, simultaneously, they open mitochondrial K(ATP) channels, thus expressing a marked antiadrenergic and antiarrhythmic effect. Another scenario, where ENK exert their modulating action, is that of heart failure (HF). In HF, acute or chronic, overexpressed ENK and their ORs provoke a cross-talk with catecholamine receptors and calcium homeostasis, depressing arrhythmogenesis and simultaneously enhancing the inotropism. In HF following an acute myocardial infarction, elevated ENK act as a biomarker, signaling the incidence of cardiorenal syndrome, increased in-hospital mortality, and recurrent infarction4. Concluding, beyond the hormonal activation referred by Singh et al¹, NEP-inhibition is expected to establish ENK as promissing cardioprotective markers, especially under conditions of ischaemia and HF.
References
1. Singh JSS, Burell LM, Cherif M, et al. Sacubitril/valsartan: beyond natriuretic peptides. Heart 2017; doi: 10.1136/ heartjnl-2017-311295.
2. Headrick JP, See Hoe LE, Du Toit EF, et al. Opioid receptors and cardioprotection- ‘opioidergic conditioning’ of the heart. Br J Pharmacol 2015; 172:2026-50.
3. Pepe S, van den Brink OW, Lakatta EG, et al. Cross-talk of opioid peptide receptor and beta-adrenergic receptor signalling in the heart. Cardiovasc Res 2004; 63:414-22.
4. Ng LL, Squire IB, Jones DJ, et al. Proenkephalin, renal dysfuntion, and prognosis in patients with acute heart failure: a GREAT network study. J Am Coll Cardiol 2017; 69:56-69.
We read with great interest this paper which demonstrated erectile dysfunction (ED), not only as a preclinical predictor of cardiovascular disease (CVD), treatment for ED. But also has a role in a reduced mortality and heart failure hospitalization1.However, a multi-country and region population-based survey indicated that the majority of Asian men have never sought treatment for ED because of cultural factors or sexual conservatism2.
Unfortunately, this situation is more serious in China. A multi-center investigation of 3327 subjects showed that although the proportion of severe cases (IIEF＜8) among the Chinese elderly is the highest in all age groups, most elderly men are reluctant to visit the hospital just for the loss of erectile function (EF). They consider the loss of libido and EF with increasing age to be a natural process of aging3. Moreover, even the old men who seek help for ED were more concerned about the side effects of Western medicine (e.g., PDE5i); only a few of them (19%) used Western medicine as the first choice4. Furthermore, Chinese physicians seldom ask patients about their sexual health during routine consultations, their neglect of the health education about ED also aggravated this vicious circle2, 4.
Hence, there is a substantial need for promoting Andersson et al 's 1 findings on health education of elderly ED patients in China. The improved awareness and cultural factors would lead more Chinese elderly to visit the hospi...
We read with great interest this paper which demonstrated erectile dysfunction (ED), not only as a preclinical predictor of cardiovascular disease (CVD), treatment for ED. But also has a role in a reduced mortality and heart failure hospitalization1.However, a multi-country and region population-based survey indicated that the majority of Asian men have never sought treatment for ED because of cultural factors or sexual conservatism2.
Unfortunately, this situation is more serious in China. A multi-center investigation of 3327 subjects showed that although the proportion of severe cases (IIEF＜8) among the Chinese elderly is the highest in all age groups, most elderly men are reluctant to visit the hospital just for the loss of erectile function (EF). They consider the loss of libido and EF with increasing age to be a natural process of aging3. Moreover, even the old men who seek help for ED were more concerned about the side effects of Western medicine (e.g., PDE5i); only a few of them (19%) used Western medicine as the first choice4. Furthermore, Chinese physicians seldom ask patients about their sexual health during routine consultations, their neglect of the health education about ED also aggravated this vicious circle2, 4.
Hence, there is a substantial need for promoting Andersson et al 's 1 findings on health education of elderly ED patients in China. The improved awareness and cultural factors would lead more Chinese elderly to visit the hospital for the loss of erectile function, and take PDE5i or other Western medicine as the preferred treatment. Then they could not only improve the quality of life, but also reduce the risk of CVD.
References:
1. Andersson DP, Trolle LY, Grotta A, Bellocco R, Lehtihet M, Holzmann MJ. Association between treatment for erectile dysfunction and death or cardiovascular outcomes after myocardial infarction. Heart. 2017-08-01 2017;103(16):1264-1270.
2. Tan HM, Low WY, Ng CJ, et al. Prevalence and correlates of erectile dysfunction (ED) and treatment seeking for ED in Asian Men: the Asian Men's Attitudes to Life Events and Sexuality (MALES) study. J Sex Med. 2007-11-01 2007;4(6):1582-1592.
3. Li D, Jiang X, Zhang X, et al. Multicenter pathophysiologic investigation of erectile dysfunction in clinic outpatients in China. Urology. 2012-03-01 2012;79(3):601-606.
4. Zhang K, Yu W, He ZJ, Jin J. Help-seeking behavior for erectile dysfunction: a clinic-based survey in China. Asian J Androl. 2014-01-01 2014;16(1):131-135.
Correspondence to Dr Dongjie Li. Department of Geriatrics, Xiangya International Medical Center, Xiangya Hospital, Central South University, Changsha 410008，China. Jerry1375@126.com.
I do welcome the systemic review and meta-analysis on drug treatment effects on outcomes in heart failure with preserved ejection fraction, by Dr Zheng and co-workers.(1) I do note the authors' definition of HFPEF as having a left ventricular ejection fraction of >40% as per the suggestions of the American Guidelines.(2) They acknowledge the difficulties posed by those with LVEF 40-49% where the evidence base is largely lacking with the exception of the more recent sub-study of CHARM data in those with LVEF in the above mid-range.(3)
I have however an issue with their inclusion of the SENIORS study data.(4) Although the mean LVEF of those labelled as HF with preserved LVEF was 49%, the patients included as those with preserved left ventricular ejection fraction, were those with LVEF>35%. This calls into question as to whether the positive effect on mortality of beta-blockers in this trial was caused by the impact of including patients with LVEF 35-40% within this group. I am sure that the authors would agree that the positive impact of the beta-blockers on the mortality of patients with LVEF 35-40%, is un-controversial.(4) While another publication from the SENIORS study group found no statistically significant difference between those deemed HFREF and those deemed HFPEF. We do know that the comparison here may be flawed for the above mentioned issue.
I would therefore, encourage the authors to reconsider their firm conclusion about the effectivenes...
I do welcome the systemic review and meta-analysis on drug treatment effects on outcomes in heart failure with preserved ejection fraction, by Dr Zheng and co-workers.(1) I do note the authors' definition of HFPEF as having a left ventricular ejection fraction of >40% as per the suggestions of the American Guidelines.(2) They acknowledge the difficulties posed by those with LVEF 40-49% where the evidence base is largely lacking with the exception of the more recent sub-study of CHARM data in those with LVEF in the above mid-range.(3)
I have however an issue with their inclusion of the SENIORS study data.(4) Although the mean LVEF of those labelled as HF with preserved LVEF was 49%, the patients included as those with preserved left ventricular ejection fraction, were those with LVEF>35%. This calls into question as to whether the positive effect on mortality of beta-blockers in this trial was caused by the impact of including patients with LVEF 35-40% within this group. I am sure that the authors would agree that the positive impact of the beta-blockers on the mortality of patients with LVEF 35-40%, is un-controversial.(4) While another publication from the SENIORS study group found no statistically significant difference between those deemed HFREF and those deemed HFPEF. We do know that the comparison here may be flawed for the above mentioned issue.
I would therefore, encourage the authors to reconsider their firm conclusion about the effectiveness of beta-blockers on the mortality of patients with HFPEF.
REFERECES:
(1). Sean Lee Zheng, Fiona T Chan, Adam A Nabeebaccus; et al. Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis. http://dx.doi.org/10.1136/heartjnl-2017-311652
(2) Yancy CW , Jessup M , Bozkurt B , et al . American College of Cardiology Foundation American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;62:e147–239
(3) ESC. 2017; https://www.escardio.org/Congresses-&-Events/Heart-Failure/Congress-reso...
(4) van Veldhuisen DJ , Cohen-Solal A , Böhm M , et al . Beta-blockade with nebivolol in elderly heart failure patients with impaired and preserved left ventricular ejection fraction: data from SENIORS (Study of effects of Nebivolol intervention on outcomes and rehospitalization in seniors with Heart failure). J Am Coll Cardiol 2009;53:2150–8
We read the study of Wei-Shiang Lin et al.[1] with a great interest. In their large-scale cohort retrospective study, they found that traumatic intracranial hemorrhage was associated with an increased risk of atrial fibrillation (AF) and hypothesized that inflammation and/or secondary cardiac insult due to the traumatic brain injury (TBI) may cause AF. Nevertheless, several points should be discussed. First, acute inflammation is well-known to be related to AF in trauma patients. The risk of new-onset AF is reasonably expected to occur at the acute phase following the trauma. This point has already been previously demonstrated to occur during the days following cardiac surgery or septic shock onset.[2] In the same way, cardiac insult occurs at the very early phase of TBI and the consecutive cardiac systolic dysfunction was reported to be reversible within the first week after the trauma. [3] In this perspective, how to explain that the risk of AF persists one year after the trauma? It would be very helpful if the authors could provide data on the delay between the day of trauma and the day of new-onset AF. Furthermore, inflammation and cardiac dysfunction are related to the TBI severity and it would be valuable to know whether the more severe TBI patients are more prone to develop AF than mild or moderate TBI. Finally, in their statistical model, the authors have taken into account comorbidities which are also known to favor AF. But others factors, such as sepsis and relat...
We read the study of Wei-Shiang Lin et al.[1] with a great interest. In their large-scale cohort retrospective study, they found that traumatic intracranial hemorrhage was associated with an increased risk of atrial fibrillation (AF) and hypothesized that inflammation and/or secondary cardiac insult due to the traumatic brain injury (TBI) may cause AF. Nevertheless, several points should be discussed. First, acute inflammation is well-known to be related to AF in trauma patients. The risk of new-onset AF is reasonably expected to occur at the acute phase following the trauma. This point has already been previously demonstrated to occur during the days following cardiac surgery or septic shock onset.[2] In the same way, cardiac insult occurs at the very early phase of TBI and the consecutive cardiac systolic dysfunction was reported to be reversible within the first week after the trauma. [3] In this perspective, how to explain that the risk of AF persists one year after the trauma? It would be very helpful if the authors could provide data on the delay between the day of trauma and the day of new-onset AF. Furthermore, inflammation and cardiac dysfunction are related to the TBI severity and it would be valuable to know whether the more severe TBI patients are more prone to develop AF than mild or moderate TBI. Finally, in their statistical model, the authors have taken into account comorbidities which are also known to favor AF. But others factors, such as sepsis and related medications are of major concerns in increasing inflammation and the risk of new-onset AF.[4] Especially, TBI patients are particularly at risk to develop sepsis in the course of disease, mainly ventilator-associated pneumonia amongst the more severe TBI patients. We think these factors should be mentioned and included in the Cox regression model.
1 Lin W-S, Lin T-C, Hung Y, et al. Traumatic intracranial haemorrhage is in association with an increased risk of subsequent atrial fibrillation. Heart Br Card Soc Published Online First: 7 April 2017. doi:10.1136/heartjnl-2016-310451
2 Meierhenrich R, Steinhilber E, Eggermann C, et al. Incidence and prognostic impact of new-onset atrial fibrillation in patients with septic shock: a prospective observational study. Crit Care Lond Engl 2010;14:R108. doi:10.1186/cc9057
3 Chaikittisilpa N, Krishnamoorthy V, Lele AV, et al. Characterizing the relationship between systemic inflammatory response syndrome and early cardiac dysfunction in traumatic brain injury. J Neurosci Res Published Online First: 2 June 2017. doi:10.1002/jnr.24100
4 Launey Y, Lasocki S, Asehnoune K, et al. Impact of Low-Dose Hydrocortisone on the Incidence of Atrial Fibrillation in Patients With Septic Shock. J Intensive Care Med 2017;:885066617696847. doi:10.1177/0885066617696847
We have read the article by dr. Ghannam with interest. We appreciate their summary of the available data on anticoagulant treatment in special patient populations. However, with the rapidly increasing evidence in this field, some recent relevant studies were not mentioned.
For instance, in patients undergoing cardioversion, the authors suggest treatment with VKA or rivaroxaban, based on the statement that this is the only available NOAC studied prospectively in this setting. Last year, the data of the ENSURE-AF with edoxaban were presented, which provide similar evidence for the use of edoxaban in this setting (1). Furthermore, the recently published EMANATE-AF study adds solid evidence for the use of apixaban in this setting (2).
Similarly, in patients undergoing catheter ablation, the RE-CIRCUIT study published earlier this year provides very reassuring prospective data on the uninterrupted use of dabigatran in patients undergoing catheter ablation (3), yet this is not mentioned in the article. At the ESC in 2017, the data of the RE-DUAL PCI study provide insight in different strategies on how to combine dabigatran with single or dual antiplatelet therapy in patients undergoing percutaneous coronary interventions (4). Similar data for rivaroxaban were described in the PIONEER study (5), and the results of the ongoing AUGUSTUS study with apixaban are expected within the next years.
In summary, the very large number of patients studied...
We have read the article by dr. Ghannam with interest. We appreciate their summary of the available data on anticoagulant treatment in special patient populations. However, with the rapidly increasing evidence in this field, some recent relevant studies were not mentioned.
For instance, in patients undergoing cardioversion, the authors suggest treatment with VKA or rivaroxaban, based on the statement that this is the only available NOAC studied prospectively in this setting. Last year, the data of the ENSURE-AF with edoxaban were presented, which provide similar evidence for the use of edoxaban in this setting (1). Furthermore, the recently published EMANATE-AF study adds solid evidence for the use of apixaban in this setting (2).
Similarly, in patients undergoing catheter ablation, the RE-CIRCUIT study published earlier this year provides very reassuring prospective data on the uninterrupted use of dabigatran in patients undergoing catheter ablation (3), yet this is not mentioned in the article. At the ESC in 2017, the data of the RE-DUAL PCI study provide insight in different strategies on how to combine dabigatran with single or dual antiplatelet therapy in patients undergoing percutaneous coronary interventions (4). Similar data for rivaroxaban were described in the PIONEER study (5), and the results of the ongoing AUGUSTUS study with apixaban are expected within the next years.
In summary, the very large number of patients studied in phase III studies, the increasing number of data from phase IV studies, and the ongoing prospective studies in specific patient situations continue to provide new data on anticoagulation therapy in situations where this was never available before. This increasing knowledge is likely to further advance the field, and algorithms as presented in this article should reflect which choices are based on clear contra-indications, and which suggestions are based on current absence of specific data, where recommendations may change based on the availability of new data.
Sincerely,
(1) Lancet. 2016 Oct 22;388(10055):1995-2003. doi: 10.1016/S0140-6736(16)31474-X. Epub 2016 Aug 30.
(2) Ezekowitz MD, et al. Late Breaking Clinical Trials 2. Presented at: European Society of Cardiology Congress; August 26-30, 2017; Barcelona, Spain
(3) Calkins H, Willems S, Gerstenfeld EP, Verma A, Schilling R, Hohnloser SH, Okumura K, Serota H, Nordaby M, Guiver K, Biss B, Brouwer MA, Grimaldi M; RE-CIRCUIT Investigators. N Engl J Med. 2017 Apr 27;376(17):1627-1636. doi: 10.1056/NEJMoa1701005. Epub 2017 Mar 19.
(4) Cannon CP, Bhatt DL, Oldgren J, Lip GYH, Ellis SG, Kimura T, Maeng M, Merkely B, Zeymer U, Gropper S, Nordaby M, Kleine E, Harper R, Manassie J, Januzzi JL, Ten Berg JM, Steg PG, Hohnloser SH; RE-DUAL PCI Steering Committee and Investigators.
(5) Gibson CM, Mehran R, Bode C, Halperin J, Verheugt FW, Wildgoose P, Birmingham M, Ianus J, Burton P, van Eickels M, Korjian S, Daaboul Y, Lip GY, Cohen M, Husted S, Peterson ED, Fox KA. N Engl J Med. 2016 Dec 22;375(25):2423-2434. doi: 10.1056/NEJMoa1611594. Epub 2016 Nov 14.
To the Editor,
We read with interest the work presented by Cahill et al. [1] in which the authors evaluate the impact of antibiotic prophylaxis to prevent bacteremia and infective endocarditis in patients undergoing dental procedures. The analysis was performed based on 36 studies, including 21 bacteremia studies, five case controls and cohort studies, and 10 time trend studies.
It is generally well established that dental cares cause bacteremia, and that most are due to streptococcal strains [1,2]. It is, consequently, reasonable to think that prescribing antibiotics before dental cares decreases the incidence of such bacteremia. Globally, the discordant results between the different kinds of studies analyzed in the paper by Cahill et al. [1] are clearly insufficient to conclude that antibiotic prophylaxis prevents bacteremia due to streptococci. In our view, this observation can be explained by the fact that dental care is not the only cause of streptococcal bacteremia. Indeed, such bacteremia are extremely common, and it has been demonstrated that they can occur after chewing and after brushing in patients with periodontitis (cumulatively in 25% and 20% of cases, respectively) [2]. It is, therefore, fairly unlikely that bacteremias due to dental cares are more responsible for endocarditis than other kinds of bacteremias. In practice, this implies that the only reasonable antibiotic prophylaxis to prevent almost every bacteremia due to oral streptococci wou...
To the Editor,
We read with interest the work presented by Cahill et al. [1] in which the authors evaluate the impact of antibiotic prophylaxis to prevent bacteremia and infective endocarditis in patients undergoing dental procedures. The analysis was performed based on 36 studies, including 21 bacteremia studies, five case controls and cohort studies, and 10 time trend studies.
It is generally well established that dental cares cause bacteremia, and that most are due to streptococcal strains [1,2]. It is, consequently, reasonable to think that prescribing antibiotics before dental cares decreases the incidence of such bacteremia. Globally, the discordant results between the different kinds of studies analyzed in the paper by Cahill et al. [1] are clearly insufficient to conclude that antibiotic prophylaxis prevents bacteremia due to streptococci. In our view, this observation can be explained by the fact that dental care is not the only cause of streptococcal bacteremia. Indeed, such bacteremia are extremely common, and it has been demonstrated that they can occur after chewing and after brushing in patients with periodontitis (cumulatively in 25% and 20% of cases, respectively) [2]. It is, therefore, fairly unlikely that bacteremias due to dental cares are more responsible for endocarditis than other kinds of bacteremias. In practice, this implies that the only reasonable antibiotic prophylaxis to prevent almost every bacteremia due to oral streptococci would be lifetime treatment with penicillin or ampicillin [3]. However, even doing so, it would be impossible to prevent all infective endocarditis, as the authors observe[1].
The main limitation of the study by Cahill et al. [1] is that it did not include negative controls for bacteremia and that the frequency of bacteremia was measured only after dental care rather than after different day-to-day situations. This is an important methodological error which makes it an unreasonable basis for justifying particular conclusions.
Thus, and for the reasons mentioned above, there is still no evidence that dental prophylaxis during dental care changes the incidence of infective endocarditis [4], and this is the only reasonable conclusion of this study.
References
[1] Cahill TJ, Harrison JL, Jewell P, Onakpoya I, Chambers JB, Dayer M, et al. Antibiotic prophylaxis for infective endocarditis: a systematic review and meta-analysis. Heart 2017;103:937–44. doi:10.1136/heartjnl-2015-309102.
[2] Forner L, Larsen T, Kilian M, Holmstrup P. Incidence of bacteremia after chewing, tooth brushing and scaling in individuals with periodontal inflammation. J Clin Periodontol 2006;33:401–7. doi:10.1111/j.1600-051X.2006.00924.x.
[3] Diene SM, Abat C, Rolain J-M, Raoult D. How artificial is the antibiotic resistance definition? Lancet Infect Dis 2017;17:690. doi:10.1016/S1473-3099(17)30338-9.
[4] Million M, Grisoli D, Griffiths K, Raoult D. Antibiotic prophylaxis of endocarditis. Lancet Infect Dis 2016;16:773–4. doi:10.1016/S1473-3099(16)30084-6.
We have read with great interest the paper “Chocolate intake and risk of clinically apparent atrial
fibrillation: the Danish Diet, Cancer, and Health Study” by Elizabeth Mostofsky and coworkers [1] and we found their conclusion of importance with a view to clinical prevention.
With reference to the findings reported in the paper, we would like to make the following contribution to the discussion. In a recent analysis performed on 650 healthy women in pre-menopausal age (age range 45-54 years) chocolate intake was higher in women in the low quartile of adherence to Mediterranean Diet (low Med Score). This subgroup of women showed a lower ABI index compared to women with higher Med Score. The analysis of sources of antioxidants showed a greater intake from fruit and vegetables in the higher quartiles of Med Score. Coffee and tea were similarly distributed among the quartiles of Med Score [2]. Analysis from diet recall had the major limitation of missing data regarding out-of-mealtime snacking and drinking.
In Mediterranean countries, wine is a strong antioxidant source and the synergistic effect of drinking wine during meals and antioxidant bioavailability is well known. We clearly understand that nutritional habits in Northern Europe differ from Mediterranean ones. However, we would like to underline that in a Mediterranean lifestyle characterized by high intake of antioxidants,...
We have read with great interest the paper “Chocolate intake and risk of clinically apparent atrial
fibrillation: the Danish Diet, Cancer, and Health Study” by Elizabeth Mostofsky and coworkers [1] and we found their conclusion of importance with a view to clinical prevention.
With reference to the findings reported in the paper, we would like to make the following contribution to the discussion. In a recent analysis performed on 650 healthy women in pre-menopausal age (age range 45-54 years) chocolate intake was higher in women in the low quartile of adherence to Mediterranean Diet (low Med Score). This subgroup of women showed a lower ABI index compared to women with higher Med Score. The analysis of sources of antioxidants showed a greater intake from fruit and vegetables in the higher quartiles of Med Score. Coffee and tea were similarly distributed among the quartiles of Med Score [2]. Analysis from diet recall had the major limitation of missing data regarding out-of-mealtime snacking and drinking.
In Mediterranean countries, wine is a strong antioxidant source and the synergistic effect of drinking wine during meals and antioxidant bioavailability is well known. We clearly understand that nutritional habits in Northern Europe differ from Mediterranean ones. However, we would like to underline that in a Mediterranean lifestyle characterized by high intake of antioxidants, chocolate represents only a small percentage with a low impact on total antioxidant intake. [3]
Moreover, It is well known that chocolate bars contain a low level of caffeine. In a previous report on hypertensive patients we found that those who reduced coffee intake had a higher chocolate bar consumption which affected total caffeine intake [3]. Due to the controversial results of the effect of caffeine on atrial fibrillation, we cannot therefore exclude the potential effects of this on arrhythmias [4].
Anna Vittoria Mattioli MD PhD, Alberto Farinetti MD, Antonio Manenti MD.
Surgical, Medical and Dental Department of Morphological Sciences related to Transplant, Oncology and Regenerative Medicine
University of Modena and Reggio Emilia (Italy)
1. Mostofsky E, Berg Johansen M, Tjønneland A, Chahal HS, Mittleman MA, Overvad K. Chocolate intake and risk of clinically apparent atrial fibrillation: the Danish Diet, Cancer, and Health Study. Heart 2017;0:1–5. doi:10.1136/heartjnl-2016-310357.
2. Mattioli AV, Pennella S, Manenti A, Migaldi M, Farinetti A. Mediterranean Diet and antioxidants intake: relationship with asymptomatic peripheral arterial disease in a population of pre-menopausal women. Abstract presented at ESC Congress August 2016
3. Mattioli AV, Farinetti A, Miloro C, Pedrazzi P, Mattioli G. Influence of coffee and caffeine consumption on atrial fibrillation in hypertensive patients. Nutr Metab Cardiovasc Dis. 2010 Feb 16. [Epub ahead of print] doi:10.1016/j.numecd.2009.11.003
4. Bhave PD, Hoffmayer K. Caffeine and atrial fibrillation: friends or foes? Heart. 2013 Oct;99(19):1377-8. doi: 10.1136/heartjnl-2013-304543.
The study of Olmos et al., on prediction of in-hospital mortality in patients with active infective endocarditis undergoing cardiac surgery, is of great interest.1
Indeed, this topic is fascinating because it is complicated to make a choice in so dramatic and not so rare situation.
To help with this decision-making, the authors proposed a model for predicting hospital mortality: a classic multivariate logistic regression model.
However, the editorial published with this article evokes in the title a new method: machine learning.2 Machine learning, which is a field of artificial intelligence, has already been used for predicting hospital mortality after elective cardiac surgery.3 This study aimed at comparing a machine learning model, a classic logistic regression model and EuroSCORE II on a cohort including 6,520 patients. The comparison of these models was based on ROC curves and decision curve analysis (DCA).4 Whatever the method of comparison, machine learning model was more accurate than other models.
Our experience in this area probably allows us to make some comments on this editorial. Considering, the increase of studies comparing machine learning with logistic regression, it is now known that supervised machine learning algorithms improve the prediction of post-operative mortality. However, the size of the cohort used in the present study makes it difficult to apply machine learning algorithms. Indeed, this cohort comprised 671 patients who...
The study of Olmos et al., on prediction of in-hospital mortality in patients with active infective endocarditis undergoing cardiac surgery, is of great interest.1
Indeed, this topic is fascinating because it is complicated to make a choice in so dramatic and not so rare situation.
To help with this decision-making, the authors proposed a model for predicting hospital mortality: a classic multivariate logistic regression model.
However, the editorial published with this article evokes in the title a new method: machine learning.2 Machine learning, which is a field of artificial intelligence, has already been used for predicting hospital mortality after elective cardiac surgery.3 This study aimed at comparing a machine learning model, a classic logistic regression model and EuroSCORE II on a cohort including 6,520 patients. The comparison of these models was based on ROC curves and decision curve analysis (DCA).4 Whatever the method of comparison, machine learning model was more accurate than other models.
Our experience in this area probably allows us to make some comments on this editorial. Considering, the increase of studies comparing machine learning with logistic regression, it is now known that supervised machine learning algorithms improve the prediction of post-operative mortality. However, the size of the cohort used in the present study makes it difficult to apply machine learning algorithms. Indeed, this cohort comprised 671 patients who had cardiac surgery, with a cohort of derivation containing only 424 patients (300 discharged alive and 124 died after surgery). This cohort was probably too small for efficient use of machine learning algorithms. However, it would have been interesting to fit a machine learning model in this field. Moreover, the fact that this database is spread over 18 years compromises the validity of this model in 2017.
In conclusion, this article and the accompanying editorial very well illustrate the current problem of artificial intelligence in medicine: how to find reliable data in sufficient quantities?
References
1 Olmos C, Vilacosta I, Habib G, et al. Risk score for cardiac surgery in active left-sided infective endocarditis. Heart 2017; 10.1136/heartjnl-2016-311093.
2 Donal E, Flecher E, Tattevin P. Machine learning to support decision-making for cardiac surgery during the acute phase of infective endocarditis. Heart Published Online First: 8 May 2017. doi:10.1136/heartjnl-2017-311512
3 Allyn J, Allou N, Augustin P, et al. A Comparison of a Machine Learning Model with EuroSCORE II in Predicting Mortality after Elective Cardiac Surgery: A Decision Curve Analysis. PloS One 2017;12:e0169772. doi:10.1371/journal.pone.0169772
4 Fitzgerald M, Saville BR, Lewis RJ. Decision curve analysis. JAMA 2015;313:409–10. doi:10.1001/jama.2015.37
The authors thank Siniorakis et al. for highlighting the cardioprotective effect of enkephalins (ENK) as well as their potential role as biomarkers in post infarct heart failure (HF).[1] We had restricted our discussion around ENK and other vasoactive peptides to allow for a broader analysis of various concepts and also to comply with article length limitations. We note that the comments of Siniorakis et al. are consistent with the objective of our article, which is to highlight the potential role of other vasoactive pathways beyond that of the natriuretic peptide system when using sacubitril / valsartan in HF.[2] Indeed there is evidence to suggest that proenkephalin may be a prognostic indicator in acute heart failure.[3]
References:
1 Siniorakis E, Arapi S, Kaplanis I, et al. Cardioprotective effects of enkephalins and potential interference from neprilysin inhibitors. [Letter to Editor], Heart 2017.
2 Singh JSS, Burrell LM, Cherif M, et al. Sacubitril/valsartan: beyond natriuretic peptides. Heart 2017.
3 Ng LL, Squire IB, Jones DJ, et al. Proenkephalin, Renal Dysfunction, and Prognosis in Patients With Acute Heart Failure: A GREAT Network Study. J Am Coll Cardiol 2017;69:56-69.
We read with great interest the recent article by Bulluck and colleagues regarding use of preoperative serum neutrophil gelatinase-associated lipocalin (sNGAL) to predict acute kidney injury (AKI) during hospitalisation and 1-year cardiovascular and all-cause mortality following adult cardiac surgery. They showed that preoperative sNGAL was an independent predictor of postoperative AKI and 1-year mortality. Although the valuable study has been actualized, two issues in methodology seem important to avoid any optimistic interpretation or misinterpretation of results.
Show MoreFirst, when using the KDIGO criteria to define and grade AKI, Bulluck et al1 used a time window of 72 h to include patients with different serum creatinine (sCr) increases from baseline, rather than 48 h, as specified by the guideline. Furthermore, it was unclear whether the sCr levels used for diagnosis and staging of AKI had been corrected based on perioperative fluid balance. The available evidence shows that not adjusting sCr levels for fluid balance may underestimate incidence of AKI after cardiac surgery, as a positive perioperative fluid balance may dilute sCr.2
Second, this study only assessed the associations of preoperative sNGAL levels with the risks of postoperative AKI and 1-year mortality, but did not provide the true predictive performances of preoperative sNGAL. To determine discriminative ability of preoperative sNGAL for adverse postoperative outcomes, the receiver operating charac...
To the Editor, Singh et al¹ refer to cardiocirculatory effects of sacubitril/valsartan beyond those related to the activation of the natriuretic peptide system. Sacubitril, by inhibiting neprilysin (NEP), upregulates various vasoactive peptides, with enkephalins (ENK) performing a major role among them. It is not by chance that PARADIGM-HF trial, which established the novel NEP inhibitor, bestows NEP with the name ‘enkephalinase’, since the latter catalyzes the degradation of ENK. Singh et al¹ concentrate on the sacubitril-related augmentation of substance P, bradykinin and adrenomedullin, while they refrain from referring to ENK. ENK and proenkephalins, their precursors, are endogenous opioids, ligands to delta and kappa opioid receptors (ORs), which are abundant in the neural system as well as in the myocardium. The endogenous opioid system exerts a significant antinociceptive action in the heart, as we deduce by observations in animal and human models². An important field where ENK have already demonstrated their cardioprotective role, is reperfusion-related ischemia, with myocardial infarction, coronary artery by pass and angioplasty constituting the principal clinical equivalents in this setting³. In all the above mentioned conditions, ENK are overexpressed, both in the neural system and locally in the myocardium. ENK action during reperfusion ischaemia is exerted via various pathways. In detail, they increase intracellular Ca²+ levels, while, simultaneously, they ope...
Show MoreWe read with great interest this paper which demonstrated erectile dysfunction (ED), not only as a preclinical predictor of cardiovascular disease (CVD), treatment for ED. But also has a role in a reduced mortality and heart failure hospitalization1.However, a multi-country and region population-based survey indicated that the majority of Asian men have never sought treatment for ED because of cultural factors or sexual conservatism2.
Show MoreUnfortunately, this situation is more serious in China. A multi-center investigation of 3327 subjects showed that although the proportion of severe cases (IIEF＜8) among the Chinese elderly is the highest in all age groups, most elderly men are reluctant to visit the hospital just for the loss of erectile function (EF). They consider the loss of libido and EF with increasing age to be a natural process of aging3. Moreover, even the old men who seek help for ED were more concerned about the side effects of Western medicine (e.g., PDE5i); only a few of them (19%) used Western medicine as the first choice4. Furthermore, Chinese physicians seldom ask patients about their sexual health during routine consultations, their neglect of the health education about ED also aggravated this vicious circle2, 4.
Hence, there is a substantial need for promoting Andersson et al 's 1 findings on health education of elderly ED patients in China. The improved awareness and cultural factors would lead more Chinese elderly to visit the hospi...
I do welcome the systemic review and meta-analysis on drug treatment effects on outcomes in heart failure with preserved ejection fraction, by Dr Zheng and co-workers.(1) I do note the authors' definition of HFPEF as having a left ventricular ejection fraction of >40% as per the suggestions of the American Guidelines.(2) They acknowledge the difficulties posed by those with LVEF 40-49% where the evidence base is largely lacking with the exception of the more recent sub-study of CHARM data in those with LVEF in the above mid-range.(3)
Show MoreI have however an issue with their inclusion of the SENIORS study data.(4) Although the mean LVEF of those labelled as HF with preserved LVEF was 49%, the patients included as those with preserved left ventricular ejection fraction, were those with LVEF>35%. This calls into question as to whether the positive effect on mortality of beta-blockers in this trial was caused by the impact of including patients with LVEF 35-40% within this group. I am sure that the authors would agree that the positive impact of the beta-blockers on the mortality of patients with LVEF 35-40%, is un-controversial.(4) While another publication from the SENIORS study group found no statistically significant difference between those deemed HFREF and those deemed HFPEF. We do know that the comparison here may be flawed for the above mentioned issue.
I would therefore, encourage the authors to reconsider their firm conclusion about the effectivenes...
We read the study of Wei-Shiang Lin et al.[1] with a great interest. In their large-scale cohort retrospective study, they found that traumatic intracranial hemorrhage was associated with an increased risk of atrial fibrillation (AF) and hypothesized that inflammation and/or secondary cardiac insult due to the traumatic brain injury (TBI) may cause AF. Nevertheless, several points should be discussed. First, acute inflammation is well-known to be related to AF in trauma patients. The risk of new-onset AF is reasonably expected to occur at the acute phase following the trauma. This point has already been previously demonstrated to occur during the days following cardiac surgery or septic shock onset.[2] In the same way, cardiac insult occurs at the very early phase of TBI and the consecutive cardiac systolic dysfunction was reported to be reversible within the first week after the trauma. [3] In this perspective, how to explain that the risk of AF persists one year after the trauma? It would be very helpful if the authors could provide data on the delay between the day of trauma and the day of new-onset AF. Furthermore, inflammation and cardiac dysfunction are related to the TBI severity and it would be valuable to know whether the more severe TBI patients are more prone to develop AF than mild or moderate TBI. Finally, in their statistical model, the authors have taken into account comorbidities which are also known to favor AF. But others factors, such as sepsis and relat...
Show MoreDear Editor,
We have read the article by dr. Ghannam with interest. We appreciate their summary of the available data on anticoagulant treatment in special patient populations. However, with the rapidly increasing evidence in this field, some recent relevant studies were not mentioned.
Show MoreFor instance, in patients undergoing cardioversion, the authors suggest treatment with VKA or rivaroxaban, based on the statement that this is the only available NOAC studied prospectively in this setting. Last year, the data of the ENSURE-AF with edoxaban were presented, which provide similar evidence for the use of edoxaban in this setting (1). Furthermore, the recently published EMANATE-AF study adds solid evidence for the use of apixaban in this setting (2).
Similarly, in patients undergoing catheter ablation, the RE-CIRCUIT study published earlier this year provides very reassuring prospective data on the uninterrupted use of dabigatran in patients undergoing catheter ablation (3), yet this is not mentioned in the article. At the ESC in 2017, the data of the RE-DUAL PCI study provide insight in different strategies on how to combine dabigatran with single or dual antiplatelet therapy in patients undergoing percutaneous coronary interventions (4). Similar data for rivaroxaban were described in the PIONEER study (5), and the results of the ongoing AUGUSTUS study with apixaban are expected within the next years.
In summary, the very large number of patients studied...
To the Editor,
Show MoreWe read with interest the work presented by Cahill et al. [1] in which the authors evaluate the impact of antibiotic prophylaxis to prevent bacteremia and infective endocarditis in patients undergoing dental procedures. The analysis was performed based on 36 studies, including 21 bacteremia studies, five case controls and cohort studies, and 10 time trend studies.
It is generally well established that dental cares cause bacteremia, and that most are due to streptococcal strains [1,2]. It is, consequently, reasonable to think that prescribing antibiotics before dental cares decreases the incidence of such bacteremia. Globally, the discordant results between the different kinds of studies analyzed in the paper by Cahill et al. [1] are clearly insufficient to conclude that antibiotic prophylaxis prevents bacteremia due to streptococci. In our view, this observation can be explained by the fact that dental care is not the only cause of streptococcal bacteremia. Indeed, such bacteremia are extremely common, and it has been demonstrated that they can occur after chewing and after brushing in patients with periodontitis (cumulatively in 25% and 20% of cases, respectively) [2]. It is, therefore, fairly unlikely that bacteremias due to dental cares are more responsible for endocarditis than other kinds of bacteremias. In practice, this implies that the only reasonable antibiotic prophylaxis to prevent almost every bacteremia due to oral streptococci wou...
Chocolate intake and risk of atrial fibrillation
Dear Editor,
We have read with great interest the paper “Chocolate intake and risk of clinically apparent atrial
fibrillation: the Danish Diet, Cancer, and Health Study” by Elizabeth Mostofsky and coworkers [1] and we found their conclusion of importance with a view to clinical prevention.
With reference to the findings reported in the paper, we would like to make the following contribution to the discussion. In a recent analysis performed on 650 healthy women in pre-menopausal age (age range 45-54 years) chocolate intake was higher in women in the low quartile of adherence to Mediterranean Diet (low Med Score). This subgroup of women showed a lower ABI index compared to women with higher Med Score. The analysis of sources of antioxidants showed a greater intake from fruit and vegetables in the higher quartiles of Med Score. Coffee and tea were similarly distributed among the quartiles of Med Score [2]. Analysis from diet recall had the major limitation of missing data regarding out-of-mealtime snacking and drinking.
Show MoreIn Mediterranean countries, wine is a strong antioxidant source and the synergistic effect of drinking wine during meals and antioxidant bioavailability is well known. We clearly understand that nutritional habits in Northern Europe differ from Mediterranean ones. However, we would like to underline that in a Mediterranean lifestyle characterized by high intake of antioxidants,...
The study of Olmos et al., on prediction of in-hospital mortality in patients with active infective endocarditis undergoing cardiac surgery, is of great interest.1
Show MoreIndeed, this topic is fascinating because it is complicated to make a choice in so dramatic and not so rare situation.
To help with this decision-making, the authors proposed a model for predicting hospital mortality: a classic multivariate logistic regression model.
However, the editorial published with this article evokes in the title a new method: machine learning.2 Machine learning, which is a field of artificial intelligence, has already been used for predicting hospital mortality after elective cardiac surgery.3 This study aimed at comparing a machine learning model, a classic logistic regression model and EuroSCORE II on a cohort including 6,520 patients. The comparison of these models was based on ROC curves and decision curve analysis (DCA).4 Whatever the method of comparison, machine learning model was more accurate than other models.
Our experience in this area probably allows us to make some comments on this editorial. Considering, the increase of studies comparing machine learning with logistic regression, it is now known that supervised machine learning algorithms improve the prediction of post-operative mortality. However, the size of the cohort used in the present study makes it difficult to apply machine learning algorithms. Indeed, this cohort comprised 671 patients who...
Pages