The letter by Dr Al-Mohammad is welcomed by the study authors and highlights some of the important challenges with using single value cut-offs for diagnosis and in determining treatment options. This is particularly true for heart failure with preserved left ventricular ejection fraction (LVEF) (HFpEF) (and more recently mid-range ejection fraction [HFmrEF], 40-49%) where decisions on starting prognostic medications can be made based on subjective echocardiographic measurements, albeit with evidence of diastolic dysfunction (tissue Doppler, flow Doppler, and volumes). Clearly, additional patient-specific factors should be taken into account, including aetiology, co-morbidities, and underlying rhythm, which are nicely highlighted in the editorial piece accompanying our study[1 2].
The Study Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors With Heart Failure (SENIORS) trial investigated the effects of the beta-blocker nebivolol in the treatment of heart failure in patients aged 70 and over[3]. Patients were required to have a clinical diagnosis of heart failure with either hospitalisation for heart failure in the previous 12 months, or a documented LVEF ≤35%. Baseline LVEF was measured by transthoracic echocardiography in 94% of cases. While van Veldhuisen et al. used an LVEF cut-off of 35% to compare “reduced” with “preserved” ejection fraction, they also examined and reported on the effect of Nebivolol in 643 patients with an LVEF ≥40%....
The letter by Dr Al-Mohammad is welcomed by the study authors and highlights some of the important challenges with using single value cut-offs for diagnosis and in determining treatment options. This is particularly true for heart failure with preserved left ventricular ejection fraction (LVEF) (HFpEF) (and more recently mid-range ejection fraction [HFmrEF], 40-49%) where decisions on starting prognostic medications can be made based on subjective echocardiographic measurements, albeit with evidence of diastolic dysfunction (tissue Doppler, flow Doppler, and volumes). Clearly, additional patient-specific factors should be taken into account, including aetiology, co-morbidities, and underlying rhythm, which are nicely highlighted in the editorial piece accompanying our study[1 2].
The Study Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors With Heart Failure (SENIORS) trial investigated the effects of the beta-blocker nebivolol in the treatment of heart failure in patients aged 70 and over[3]. Patients were required to have a clinical diagnosis of heart failure with either hospitalisation for heart failure in the previous 12 months, or a documented LVEF ≤35%. Baseline LVEF was measured by transthoracic echocardiography in 94% of cases. While van Veldhuisen et al. used an LVEF cut-off of 35% to compare “reduced” with “preserved” ejection fraction, they also examined and reported on the effect of Nebivolol in 643 patients with an LVEF ≥40%. Results for this subgroup were included in our meta-analysis, ensuring that all patients included in our meta-analysis had an ejection fraction greater than this. Of note, inclusion of an additional 109 patients with an LVEF of 35-40% had minimal effect on the primary composite outcome of all-cause mortality or cardiovascular hospitalisation (LVEF ≥35%: HR 0.81, NS; LVEF ≥40%: HR 0.82, NS), or all-cause mortality (LVEF ≥35%: HR 0.91, NS; LVEF ≥40%: HR 0.92, NS). Indeed in SENIORS, the point estimate for reduction in the primary outcome was greater in those with an LVEF ≥40% (HR 0.82, NS) than in those with LVEF ≤35% (HR 0.86, NS).
We have tentatively concluded that beta-blockers may be of benefit in HFpEF, on the basis of pooled analysis from 3 trials, enrolling just 1046 participants. A large propensity-matched study from the Swedish Heart Failure registry (8244 patients) mirrored these findings with a 7% reduction in all-cause mortality at 5 years (P=0.04)[4]. Results from an individual patient data meta-analysis of beta-blockers in heart failure were recently presented at the European Society of Cardiology Congress and suggested reductions in all-cause and cardiovascular mortality in patients with HFmrEF (LVEF 40 to 49%) and sinus rhythm, but not in HFpEF (LVEF ≥50%) with sinus rhythm[5]. This study importantly highlights the importance of additional patient characteristics such as underlying rhythm. There is currently insufficient evidence to recommend widespread use of beta-blockers in HFpEF, and large prospective randomised controlled trial using a beta-blocker of proven benefit in reduced ejection fraction (e.g. bisoprolol, carvedilol, metoprolol[6]) is needed. It will be critically important to untangle and identify which specific patients with HFpEF may benefit from beta-blocker therapy.
1. Zheng SL, Chan FT, Nabeebaccus AA, et al. Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis. Heart 2017 doi: 10.1136/heartjnl-2017-311652published Online First: Epub Date]|.
2. Schnell F, Donal E. Pharmacological strategies in heart failure with preserved ejection fraction: time for an individualised treatment strategy? Heart 2017 doi: 10.1136/heartjnl-2017-312119published Online First: Epub Date]|.
3. van Veldhuisen DJ, Cohen-Solal A, Bohm 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). Journal of the American College of Cardiology 2009;53(23):2150-58 doi: http://dx.doi.org/10.1016/j.jacc.2009.02.046published Online First: Epub Date]|.
4. Lund LH, Benson L, Dahlstrom U, Edner M, Friberg L. Association between use of beta-blockers and outcomes in patients with heart failure and preserved ejection fraction. Jama 2014;312(19):2008-18 doi: 10.1001/jama.2014.15241published Online First: Epub Date]|.
5. Kotecha D. Efficacy of beta-blockers in heart failure according to left ventricular ejection fraction: An individual patient level analysis of double-blind randomised trials. Secondary Efficacy of beta-blockers in heart failure according to left ventricular ejection fraction: An individual patient level analysis of double-blind randomised trials 2017. http://congress365.escardio.org/Presentation/162249 - .WbHKsNOGMWo.
6. Chatterjee S, Biondi-Zoccai G, Abbate A, et al. Benefits of beta blockers in patients with heart failure and reduced ejection fraction: network meta-analysis. BMJ (Clinical research ed.) 2013;346:f55 doi: 10.1136/bmj.f55published Online First: Epub Date]|.
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.
We thank Xue et al for their interest in our article (1). The KDIGO classification (2) comprises 3 criteria in the diagnosis of acute kidney injury (AKI), namely an increase in serum creatinine (SCr) by ≥0.3 mg/dl (≥26.5 μmol/l) within 48 hours; or an increase in SCr to ≥1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or urine volume <0.5 ml/kg/h for 6 hours. In our study, we had collected serial blood samples for the first 72 hours and the second KDIGO criterion (an increase in SCr to ≥1.5 times baseline) was applied over the 72 hours period to assess for AKI. As for the impact of perioperative fluid balance, this is not currently part of the recommendation, and the available evidence quoted (3) was taken from a retrospective, single-center study using the AKIN classification for AKI. Unfortunately the perioperative fluid balance was not collected in our study and we could not take this into account.
We did look at the Receiver Operating Characteristic curve analysis using sNGAL as a continuous variable. The area under the curve (AUC) was 0.57 (95%CI 0.54-0.60), very similar to that of sNGAL tertiles reported in our paper.(1) The diagnostic performance of sNGAL alone was quite low and therefore we did not provide cut-off values/sensitivity/specificity and predictive values. Expressing sNGAL as quartiles is more practical from a clinical point of view and we showed that by adding clinical factors, the c-statistic improved...
We thank Xue et al for their interest in our article (1). The KDIGO classification (2) comprises 3 criteria in the diagnosis of acute kidney injury (AKI), namely an increase in serum creatinine (SCr) by ≥0.3 mg/dl (≥26.5 μmol/l) within 48 hours; or an increase in SCr to ≥1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or urine volume <0.5 ml/kg/h for 6 hours. In our study, we had collected serial blood samples for the first 72 hours and the second KDIGO criterion (an increase in SCr to ≥1.5 times baseline) was applied over the 72 hours period to assess for AKI. As for the impact of perioperative fluid balance, this is not currently part of the recommendation, and the available evidence quoted (3) was taken from a retrospective, single-center study using the AKIN classification for AKI. Unfortunately the perioperative fluid balance was not collected in our study and we could not take this into account.
We did look at the Receiver Operating Characteristic curve analysis using sNGAL as a continuous variable. The area under the curve (AUC) was 0.57 (95%CI 0.54-0.60), very similar to that of sNGAL tertiles reported in our paper.(1) The diagnostic performance of sNGAL alone was quite low and therefore we did not provide cut-off values/sensitivity/specificity and predictive values. Expressing sNGAL as quartiles is more practical from a clinical point of view and we showed that by adding clinical factors, the c-statistic improved to 0.69. We are aware that the value of 0.69 is not ideal for clinical application and our work was a post-hoc analysis of a randomized controlled trial (4) consisting of high-risk patients (EuroSCORE≥5). Therefore, further work remains to be done in a larger number of all-comers going for cardiac surgery to improve the identification of patients at risk of AKI.
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 doi: 10.1136/heartjnl-2017-311760
2. James M, Bouchard J, Ho J, et al. Canadian Society of Nephrology commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury. American journal of kidney diseases : the official journal of the National Kidney Foundation 2013;61(5):673-85. doi: 10.1053/j.ajkd.2013.02.350
3. 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. Journal of cardiothoracic and vascular anesthesia 2015;29(5):1229-35. doi: 10.1053/j.jvca.2015.02.004
4. Hausenloy DJ, Candilio L, Yellon DM. Remote Ischemic Preconditioning and Cardiac Surgery. The New England journal of medicine 2016;374(5):491-2.
Dear Editor,
With great interest, I read the article by Sainsbury and associates[1] and congratulate them for extensively reviewing the unsolved issue of refractory angina. How many suffer from this condition worldwide remains unclear. However, it is believed that hundreds of thousands of Americans are affected, and that this number increases annually. Likely, millions are affected worldwide. Diffuse coronary artery disease is the main reason for refractory angina, because such arteries are non-amenable to percutaneous interventions or bypass grafting. Comorbidities are a second reason, especially in our aging population. Yet history is a cycle; medicine’s history no exception. Old concept, experiments, and theories that have fallen by the wayside can sometimes be resurrected and re-explored, released from the technological constraints of their time. The coronary sinus reducer system is one good example, since the concept stems from studies on the effects of cardiac vein ligation performed in the 1930s by Canadian surgeon Mercier Fauteux[2]. Two additional concepts might be resurrected and adapted to modern technologies. One is the concept of internal mammary artery (IMA) occlusion which, at that time, was performed through a small bilateral incision between the second and third ribs. The belief was that localized hypertension superior to the obstruction increased perfusion pressure in channels leading to the heart, specifically through the peri-cardio-phrenic br...
Dear Editor,
With great interest, I read the article by Sainsbury and associates[1] and congratulate them for extensively reviewing the unsolved issue of refractory angina. How many suffer from this condition worldwide remains unclear. However, it is believed that hundreds of thousands of Americans are affected, and that this number increases annually. Likely, millions are affected worldwide. Diffuse coronary artery disease is the main reason for refractory angina, because such arteries are non-amenable to percutaneous interventions or bypass grafting. Comorbidities are a second reason, especially in our aging population. Yet history is a cycle; medicine’s history no exception. Old concept, experiments, and theories that have fallen by the wayside can sometimes be resurrected and re-explored, released from the technological constraints of their time. The coronary sinus reducer system is one good example, since the concept stems from studies on the effects of cardiac vein ligation performed in the 1930s by Canadian surgeon Mercier Fauteux[2]. Two additional concepts might be resurrected and adapted to modern technologies. One is the concept of internal mammary artery (IMA) occlusion which, at that time, was performed through a small bilateral incision between the second and third ribs. The belief was that localized hypertension superior to the obstruction increased perfusion pressure in channels leading to the heart, specifically through the peri-cardio-phrenic branch[3]. Recently, I have resurrected this concept and suggested performing endovascular occlusion of the IMAs[4]. More recently, others have demonstrated that occluding the IMAs arteries could increase the collateral flow index and fractional flow reserve ipsilaterally, while decreasing angina[5]. These data are encouraging and spur further investigations. However, I also feel that Vineberg’s operation, consisting of tunnelization of IMAs into the left ventricle wall, is worthy of resurrection. This procedure, performed for about two decades, once was successful at relieving angina[2]. A huge collateral network developed between the IMAs and coronary arteries, and the IMAs often remained patent even at long-term follow-up. There is no reason to a-priori exclude IMA intra-myocardial tunnelization in patients for whom bypass is contraindicated, and vast opportunities exist for novel experimental and clinical studies on this technique.
Words = 345
References
1. Sainsbury PA, Fisher M, de Silva R. Alternative interventions for refractory angina. Heart. 2017 ;103(23):1911-1922.
2. Picichè M. The history of myocardial revascularization before the advent of cardiopulmonary bypass, in: M. Picichè (Ed.), Dawn and Evolution of Cardiac Procedures:Research Avenues in Cardiac Surgery and Interventional Cardiology, Springer- Verlag, Heidelberg 2012, pp. 65–77.
3. Picichè M. Noncoronary Collateral Myocardial Blood Flow: The Human Heart’s Forgotten Blood Supply. The Open Cardiovasc Med J 2015; 9:105-113.
4. Picichè M. Embolization of the internal thoracic arteries in refractory angina. Int J Cardiol. 2016;212:310.
5. Stoller M, Seiler C. Effect of permanent right internal mammary artery closure on coronary collateral function and myocardial ischemia. Circ Cardiovasc Interv 2017;10:e004990.
Title of E-letter: Intra coronary imaging to detect mal apposition: Are We Seeing Too Much!
Authors Name: Dr Yasir Parviz
Institution: Columbia University Medical Center
Intracoronary Imaging Heart 2017; 0: heartjnl-2015-307888v1
Link to the original paper: http://hwmaint.heart.bmj.com/cgi/content/full/heartjnl-2015-307888v1
Main Text:
We would like to congratulate Giavarini A et al on this comprehensive, educational article on intracoronary imaging. [1] Various modalities can be used to understand the mechanism of stent failure, and there is an ongoing debate on detection of stent mal-apposition, and whether this has any clinical impact. Acute stent mal-apposition on its own is not associated with adverse clinical events unless associated with under expansion or having inflow- outflow issues. Acute mal-apposition and its associated clinical events are possibly reduced due to negative remodelling.[2] The clinically events are non-significant may be due to the fact that newer generation of stents and stronger antiplatelets are performing very well. There is limited literature evidence to support that acute mal-apposition is associated with stent thrombosis. [3] Late acquired malaposition in combination with other contributing factors can be associated with stent failure. Most of the available literature looking into the mechanism of stent failure is from...
Title of E-letter: Intra coronary imaging to detect mal apposition: Are We Seeing Too Much!
Authors Name: Dr Yasir Parviz
Institution: Columbia University Medical Center
Intracoronary Imaging Heart 2017; 0: heartjnl-2015-307888v1
Link to the original paper: http://hwmaint.heart.bmj.com/cgi/content/full/heartjnl-2015-307888v1
Main Text:
We would like to congratulate Giavarini A et al on this comprehensive, educational article on intracoronary imaging. [1] Various modalities can be used to understand the mechanism of stent failure, and there is an ongoing debate on detection of stent mal-apposition, and whether this has any clinical impact. Acute stent mal-apposition on its own is not associated with adverse clinical events unless associated with under expansion or having inflow- outflow issues. Acute mal-apposition and its associated clinical events are possibly reduced due to negative remodelling.[2] The clinically events are non-significant may be due to the fact that newer generation of stents and stronger antiplatelets are performing very well. There is limited literature evidence to support that acute mal-apposition is associated with stent thrombosis. [3] Late acquired malaposition in combination with other contributing factors can be associated with stent failure. Most of the available literature looking into the mechanism of stent failure is from IVUS studies and newer technology, OCT due to superior resolution has the ability to detect a higher percentage of mal appositions.[4] There is on-going research on to the clinical significance of these findings.
We are presenting a summary of some evidence in detection of malapposition by IVUS /OCT and its clinical impact.
1)Im et al. Circ Cardiovasc Interv 2014;7:88-96.
356(n),62%(OCT), no impact.
2)Kubo et al. JACCCardiovasc Imaging 2013;6:1095-104.
100(n), 14%(IVUS), 39%(OCT), no impact
3)Kawamori et al. EHJ Cardiovasc Imaging 2013;14:865-75.
40(n), 65%(OCT), no impact
4)Bezerra et al. JACC Cardiovasc Interv 2013;6:228-36
26(n), 42% (IVUS), 96%(OCT), no impact
5)Ali ZA et al Lancet. 2016 Nov 26;388(10060):2618-2628.
304(n), 39% (IVUS), 41% OCT, no impact
6)Prati et al JACC Cardiovascular Imaging November 2015 2015;8:1297.
832(n), 50%(OCT), no impact
7)Prati F et al Am Heart J. 2015 Feb;169(2):249-56.
63(n), 52%(OCT), no impact
8)Hong et al, Circulation. 2006;113:414-9.
557(n), 12 %(IVUS),no impact
9)Steinberg et al J Am Coll Cardiol Intv 3:486-494.
1580(n), 7-10%(IVUS), no impact
10)Soeda et al Circulation. 2015 Sep 15;132(11):1020-9.
786(n), 39%(OCT), no impact
11)Kimura M Am J Cardiol. 2006;98:436-442.
168(n) 77% (IVUS), no impact
References.
1.Giavarini A, Kilic ID, Redondo Dieguez A, Longo G, Vandormael I, Pareek N, Kanyal R, De Silva R and Di Mario C. Intracoronary Imaging. Heart. 2017.
2. Guo N, Maehara A, Mintz GS, He Y, Xu K, Wu X, Lansky AJ, Witzenbichler B, Guagliumi G, Brodie B, Kellett MA, Jr., Dressler O, Parise H, Mehran R and Stone GW. Incidence, mechanisms, predictors, and clinical impact of acute and late stent malapposition after primary intervention in patients with acute myocardial infarction: an intravascular ultrasound substudy of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial. Circulation. 2010;122:1077-84.
3. Alfonso F, Suarez A, Angiolillo DJ, Sabate M, Escaned J, Moreno R, Hernandez R, Banuelos C and Macaya C. Findings of intravascular ultrasound during acute stent thrombosis. Heart. 2004;90:1455-9.
4. Ali ZA, Maehara A, Genereux P, Shlofmitz RA, Fabbiocchi F, Nazif TM, Guagliumi G, Meraj PM, Alfonso F, Samady H, Akasaka T, Carlson EB, Leesar MA, Matsumura M, Ozan MO, Mintz GS, Ben-Yehuda O, Stone GW and Investigators IIOP. Optical coherence tomography compared with intravascular ultrasound and with angiography to guide coronary stent implantation (ILUMIEN III: OPTIMIZE PCI): a randomised controlled trial. Lancet. 2016;388:2618-2628.
Honarbakhsh et al should be congratulated upon their innovative
research in improving the care for patients with arrhythmias. Their paper
not only demonstrates an effective community treatment strategy but
importantly is cost effective during the current austerity. Potential
further cost savings and enhanced patient experiences could be anticipated
by encouraging General Practitioners to subsequently refer patients
wishi...
Honarbakhsh et al should be congratulated upon their innovative
research in improving the care for patients with arrhythmias. Their paper
not only demonstrates an effective community treatment strategy but
importantly is cost effective during the current austerity. Potential
further cost savings and enhanced patient experiences could be anticipated
by encouraging General Practitioners to subsequently refer patients
wishing for a curative strategy directly to Electrophysiologists for
consideration of an ablation.
Patients affected by SVTs usually experience frustrating recurrent
attendances at Accident and Emergency departments prior to referral to
Electrophysiologists, despite our knowledge that ablations are successful
in 95% at the first procedure. Similarly, many journeys to the AED are
aborted as the symptoms self terminate prior to arrival or have abated by
the time of medical review. Thus frequently ECGs fail to capture their
arrhythmia and clinch the diagnosis, protracting the time to effective
treatment.
The PARA group had a statistically significant greater chance of receiving
a copy of their ECG (85% v 63%, p-value 0.035) and therefore this often
illusive information would have a greater chance of being available for
inclusion in the onward referral to the Cardiologist or
Electrophysiologist.
Partnerships between community and tertiary care services can
expedite and improve arrhythmia care, reducing some of the burden on over
stretched Emergency Departments.
Authors mentioned, that meta-analysis include both published and unpublished data from randomised controlled trials (this remove bias of selective clinical trial reporting), and results were regardless of background statin or combination laropiprant therapy ( to maintain clarity, and or to remove confusion with regards to results). 34% higher risk of developing diabetes was reported with Niacin therapy and new-onset diabetes i...
Authors mentioned, that meta-analysis include both published and unpublished data from randomised controlled trials (this remove bias of selective clinical trial reporting), and results were regardless of background statin or combination laropiprant therapy ( to maintain clarity, and or to remove confusion with regards to results). 34% higher risk of developing diabetes was reported with Niacin therapy and new-onset diabetes is a major concern (1), however diabetogenic effect of statins is difficult to ignore in patients. Niacin (nicotinic acid) reduces cardiovascular events in patients with dyslipidemia also a cause of vasodilation, and Laropiprant is a selective antagonist of the prostaglandin D2 receptor subtype 1 (DP1), was effective in suppressing both subjective and objective manifestations of niacin-induced vasodilation [2], combintion still in use in the USA and elsewhere but Merck withdraws Tredaptive in Europe & globally (1).
I read the article with great interest.
With Regards, Dr.Rajiv Kumar Professor, Pharmacology Department. Goverment Medical College & Hospital,Chandigarh- 160030, India.
References:
1.Christina Goldie, Allen J Taylor, Peter Nguyen, Cody McCoy, Xue-Qiao Zhao, David Preiss. Niacin therapy and the risk of new-onset diabetes: a meta-analysis of randomised controlled trials . Heart Published Online First: 14 September 2015 doi:10.1136/heartjnl-2015-308055.
2.Lai E, De Lepeleire I, Crumley TM et al. "Suppression of niacin-induced vasodilation with an antagonist to prostaglandin D2 receptor subtype 1". Clin. Pharmacol. Ther. 2007; 81(6): 849-57.
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.
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.
The letter by Dr Al-Mohammad is welcomed by the study authors and highlights some of the important challenges with using single value cut-offs for diagnosis and in determining treatment options. This is particularly true for heart failure with preserved left ventricular ejection fraction (LVEF) (HFpEF) (and more recently mid-range ejection fraction [HFmrEF], 40-49%) where decisions on starting prognostic medications can be made based on subjective echocardiographic measurements, albeit with evidence of diastolic dysfunction (tissue Doppler, flow Doppler, and volumes). Clearly, additional patient-specific factors should be taken into account, including aetiology, co-morbidities, and underlying rhythm, which are nicely highlighted in the editorial piece accompanying our study[1 2].
Show MoreThe Study Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors With Heart Failure (SENIORS) trial investigated the effects of the beta-blocker nebivolol in the treatment of heart failure in patients aged 70 and over[3]. Patients were required to have a clinical diagnosis of heart failure with either hospitalisation for heart failure in the previous 12 months, or a documented LVEF ≤35%. Baseline LVEF was measured by transthoracic echocardiography in 94% of cases. While van Veldhuisen et al. used an LVEF cut-off of 35% to compare “reduced” with “preserved” ejection fraction, they also examined and reported on the effect of Nebivolol in 643 patients with an LVEF ≥40%....
I read with interest the bright review of stable coronary syndromes (1). In the formation of the fetal muscular part
of the interventricular septum (IVS), the expanding ventricles grow and their medial walls approach and fuse, forming
the septum. The inside corner between the septum and the right anterior ventricular wall exhibits the deep pits being
called interventricular sinuses (ISs). The IS passes through the right IVS formed from the medial wall of the expanding
fetal right ventricle (RV). The opening of the interventricular vessel (IV) (kuuselian vessel) is located in the IS between
the medial walls of the expanding fetal RV and fetal left ventricle (LV). The IV is not a canal or channel or blood
vessel, but a slit between the fibres of the muscle to the outer layer of the left central muscular part of the IVS and runs
at an angle of about 90 degrees through sphincter and the left IVS into the LV. The IV exhibits 2 to 3 oval 2x5 mm
openings in the left central muscular part of the IVS surrounded by the interventricular sphincter (ISP). The ISP and the
IV are feasible to be patent by relaxing and widening of the helical heart at the right atrial filling phase at the end of the
fetal diastole. The left to right communication do not result as the earliest left ventricular activation close the ISP. The
sinoatrial node initially activates the right atrium (RA), followed by activation...
Show MoreWe 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...
We thank Xue et al for their interest in our article (1). The KDIGO classification (2) comprises 3 criteria in the diagnosis of acute kidney injury (AKI), namely an increase in serum creatinine (SCr) by ≥0.3 mg/dl (≥26.5 μmol/l) within 48 hours; or an increase in SCr to ≥1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or urine volume <0.5 ml/kg/h for 6 hours. In our study, we had collected serial blood samples for the first 72 hours and the second KDIGO criterion (an increase in SCr to ≥1.5 times baseline) was applied over the 72 hours period to assess for AKI. As for the impact of perioperative fluid balance, this is not currently part of the recommendation, and the available evidence quoted (3) was taken from a retrospective, single-center study using the AKIN classification for AKI. Unfortunately the perioperative fluid balance was not collected in our study and we could not take this into account.
Show MoreWe did look at the Receiver Operating Characteristic curve analysis using sNGAL as a continuous variable. The area under the curve (AUC) was 0.57 (95%CI 0.54-0.60), very similar to that of sNGAL tertiles reported in our paper.(1) The diagnostic performance of sNGAL alone was quite low and therefore we did not provide cut-off values/sensitivity/specificity and predictive values. Expressing sNGAL as quartiles is more practical from a clinical point of view and we showed that by adding clinical factors, the c-statistic improved...
Dear Editor,
Show MoreWith great interest, I read the article by Sainsbury and associates[1] and congratulate them for extensively reviewing the unsolved issue of refractory angina. How many suffer from this condition worldwide remains unclear. However, it is believed that hundreds of thousands of Americans are affected, and that this number increases annually. Likely, millions are affected worldwide. Diffuse coronary artery disease is the main reason for refractory angina, because such arteries are non-amenable to percutaneous interventions or bypass grafting. Comorbidities are a second reason, especially in our aging population. Yet history is a cycle; medicine’s history no exception. Old concept, experiments, and theories that have fallen by the wayside can sometimes be resurrected and re-explored, released from the technological constraints of their time. The coronary sinus reducer system is one good example, since the concept stems from studies on the effects of cardiac vein ligation performed in the 1930s by Canadian surgeon Mercier Fauteux[2]. Two additional concepts might be resurrected and adapted to modern technologies. One is the concept of internal mammary artery (IMA) occlusion which, at that time, was performed through a small bilateral incision between the second and third ribs. The belief was that localized hypertension superior to the obstruction increased perfusion pressure in channels leading to the heart, specifically through the peri-cardio-phrenic br...
Title of E-letter: Intra coronary imaging to detect mal apposition: Are We Seeing Too Much!
Authors Name: Dr Yasir Parviz
Institution: Columbia University Medical Center
Intracoronary Imaging Heart 2017; 0: heartjnl-2015-307888v1
Link to the original paper: http://hwmaint.heart.bmj.com/cgi/content/full/heartjnl-2015-307888v1
Main Text:
We would like to congratulate Giavarini A et al on this comprehensive, educational article on intracoronary imaging. [1] Various modalities can be used to understand the mechanism of stent failure, and there is an ongoing debate on detection of stent mal-apposition, and whether this has any clinical impact. Acute stent mal-apposition on its own is not associated with adverse clinical events unless associated with under expansion or having inflow- outflow issues. Acute mal-apposition and its associated clinical events are possibly reduced due to negative remodelling.[2] The clinically events are non-significant may be due to the fact that newer generation of stents and stronger antiplatelets are performing very well. There is limited literature evidence to support that acute mal-apposition is associated with stent thrombosis. [3] Late acquired malaposition in combination with other contributing factors can be associated with stent failure. Most of the available literature looking into the mechanism of stent failure is from...
Show MoreHonarbakhsh et al should be congratulated upon their innovative research in improving the care for patients with arrhythmias. Their paper not only demonstrates an effective community treatment strategy but importantly is cost effective during the current austerity. Potential further cost savings and enhanced patient experiences could be anticipated by encouraging General Practitioners to subsequently refer patients wishi...
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 MoreThe 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.
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