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Recent eLetters

Displaying 1-10 letters out of 648 published

  1. PATIENT-PROSTHESIS MISMATCH IN PATIENTS UNDER 70 YEARS OF AGE: DOES IT HAVE AN IMPACT ON SURVIVAL BUT NOT ON VENTRICULAR MASS REGRESSION?

    Left ventricular (LV) hypertrophy caused by severe aortic stenosis is highly associated with sudden death, congestive heart failure and stroke. After aortic valve replacement (AVR) the pressure gradient between the left ventricle and ascending aorta decreases and reverse left ventricular modeling begins to appear. However, if a certain degree of residual aortic stenosis remains, reverse modeling may be compromised which can affect clinical outcomes. With great interest, we read the article by Price J and associates1 on the importance of age as a modifier of the relationship between patient-prosthesis mismatch (PPM) and outcomes. Although this article tries to clarify the controversy around this issue, the results are, in absence of an explanation, contradictory in themselves. These conclusions1 may be summarized in: 1. In patients older than 70 years of age, PPM reduced the LV mass index (LVMI) regression in patients with LV dysfunction but not in those with normal LV function. Conversely, PPM had no effect on death or congestive heart failure regardless of LV function. 2. In patients under 70 years of age, PPM did not reduce LVMI regression regardless of LV function. Conversely, PPM was associated with increased death or congestive heart failure in patients with LV dysfunction but not in those with normal LV function. Therefore, it seems that LVMI regression and clinical outcomes are two independent circumstances when intuitively one should cause the other. At this point, we would like to note that, although there are several ways to detect PPM, only two have been considered acceptable in the last years.2 One way is to perform an echocardiography for each patient several months after the intervention. This method has some limitations due to technical difficulties in measurements of echocardiography. Moreover, it is impossible to know if those patients who dye before the echocardiography have mismatch, being precisely these echocardiograms those that could provide more relevant information. Probably due to these limitations, Price J et al.1 opted for the use of tables derived from the literature. However, one must be aware that this method cannot detect all patients with PPM, and there are false-positive and false-negative categorizations.3 Bleiziffer et al.2 demonstrated that the sensitivity and specificity to detect PPM are 71% and 67% when using echocardiographically derived reference tables. Hence, estimations of PPM based on reference tables yield low sensitivity and specificity, leading to incorrect categorization of patients. This effect of false categorization might outweigh that of inaccurate echocardiographic measurements because the effective orifice area of the same prosthesis can vary widely among patients.3 Therefore, so far we have not found the perfect way to detect PPM. This circumstance can explain the contradictory results observed by Price J et al.1 and is probably the main reason why after almost 40 years of research4 we continue to discuss the clinical relevance of a residual aortic stenosis in our postoperative patients. REFERENCES 1. Price J, Toeg H, Lam BK et al. The impact of prosthesis-patient mismatch after aortic valve replacement varies according to age at operation. Heart. 2014;100:1099-106. 2. Bleiziffer S1, Eichinger WB, Hettich I et al. Prediction of valve prosthesis-patient mismatch prior to aortic valve replacement: which is the best method? Heart. 2007;93:615-20. 3. Bleiziffer S, Eichinger WB, Lange R. Letter by Bleiziffer et al regarding article, "Long-term outcomes after valve replacement for low-gradient aortic stenosis: impact of prosthesis-patient mismatch". Circulation. 2006;114:e627. 4. Rahimtoola SH. The problem of valve prosthesis-patient mismatch. Circulation. 1978;58:20-4

    Conflict of Interest:

    None declared

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  2. Promising for prognostic evaluation but cost-effectiveness and frequency of monitoring require consideration

    Firstly, looking at the study design the selected age range of HCM subjects (mean age of 56 years) may at least in part account for the high percentage of myocardial fibrosis at baseline (66 %) as in addition to the fibrosis likely being a pathological consequence of HCM itself, this age group of participants may harbour occult or sub-clinical coronary artery disease and a prior association between cardiac ischemia and myocardial fibrosis has been reported in the literature (1).

    While these findings theoretically justify the use of routine cardiac MRI at the time of HCM diagnosis in conjunction with echocardiography (enabling the detection of two predictive variables of sudden cardiac death, fibrosis and left ventricular ejection fraction, respectively) as a comprehensive diagnostic work-up, this consideration needs to be carefully balanced against the economic burden of widely implementing such sophisticated imaging and the realisation that such techniques do not exist widely in all centres for effective risk stratification to take place on a national level (2).

    Finally, the question remains as to what represents an appropriate time interval for monitoring the progression of myocardial fibrosis once already detected and how this will be determined? This may be of particular importance as you have established that the extent of myocardial fibrosis (if we place this irreversible process along a continuum) was a statistically significant predictor of sudden cardiac death. Thus, if the fibrotic process wasn't monitored linearly over time in these patients, and the myocardial fibrosis was detected once already 'extensive', the risk of sudden cardiac death in this subset of HCM subjects may remain high despite any prevailing medical or surgical intervention.

    References:-

    1) Wilson JM, Villareal RP, Hariharan R, Massumi A, Muthupillai R, Flamm SD. Magnetic Resonance Imaging of Myocardial Fibrosis in Hypertrophic Cardiomyopathy (2002). Tex Heart Inst J.29:176-180.

    2) To ACY, Dhillon A, Desai MY. Cardiac Magnetic Resonance in Hypertrophic Cardiomyopathy (2011). J Am Coll Cardiol Img. 4(10):1123- 1137.

    Conflict of Interest:

    None declared

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  3. Cardiac Troponin T assay is not cardiac specific.

    The authors have compared clinical outcomes between the use of a conventional cardiac Troponin I ( cTnI) assay and a high sensitivity cardiac Troponin T (hs-cTnT)assay. They conclude that the introduction of the hs-cTnT assay did not influence outcomes at 6 months. Their conclusions might have been different if they had compared a conventional cTnI assay with a hs-cTnI assay. We now know that there are major differences between cTnI and cTnT assays (1). The cTnT protein , unlike its cTnI counterpart, is found in both myocardium and diseased skeletal muscle. The Roche cTnT assay cannot distinguish between cTnT from myocardium and re-expressed cTnT found in diseased skeletal muscle (2). Elevated cTnT in the circulation can have dual significance, myocardial or skeletal muscle injury. Patients with several different types of acquired or inherited skeletal muscle diseases have persistent elevation of cTnT without clinical or cTnI evidence of myocardial injury. It has also been shown that elevation of cTnT in these patients has no adverse impact on cardiovascular outcomes. The use of hs-cTnT has made the problem of cardiac specificity worse as it identifies low levels of elevated cTnT in additional patients with skeletal muscle diseases, which would not have been detected by standard cTnT assay. It should also be noted that many of these patients have subclinical skeletal myopathies. It is currently unknown what proportion of patients attending the emergency department with chest pain have elevated cTnT due to skeletal muscle diseases, not myocardial injury. It would be interesting if the authors were able to re-analyse any stored samples they may have with hs- cTnI.

    1.Rittoo D, Jones A, Lecky B, Neithercut D . Elevation of cardiac troponin T, but not cardiac troponin I, in patients with neuromuscular diseases: implications for the diagnosis of myocardial infarction. J Am Coll Cardiol. 2014 Jun 10;63(22):2411-20.

    2.Jaffe AS, Vasile VC, Milone M, Saenger AK, Olson KN, Apple FS. Diseased skeletal muscle: a noncardiac source of increased circulating concentrations of cardiac troponin T. J Am Coll Cardiol. 2011 Oct 18;58(17):1819-24.

    Conflict of Interest:

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  4. Right ventricular stroke work in children with pulmonary arterial hypertension: a promising approach

    We read with great interest the article by Di Maria et al. [1], describing the importance of right ventricular (RV) performance, especially RV stroke work (RVSW) in children with pulmonary arterial hypertension (PAH). The authors investigated the relation between echocardiographic measurements of RV function and the "gold standard" of right heart catheterization in children and found that the RVSW strongly correlates with non-invasive data of RV function [1]. The authors concluded that RVSW correlates with outcome parameters, e.g. abnormal WHO class, and mortality, in children with PAH. We completely agree with the findings of Di Maria et al. [1] and want to emphasize the importance of echocardiographic evaluation, e.g. tricuspid annular peak systolic excursion (TAPSE) for longitudinal management of pediatric patients with PAH. Di Maria et al. compared data of patients with adverse outcomes to patients with WHO class I-III, of different age groups: median 16.9 versus 11.8 years (table 1) and found no statistically significant difference of TAPSE (mean values 1.3 versus 1.5 cm, respectively) between those groups [1]. In our opinion their data would have been more promising and statistically significant, if the authors would have compared their TAPSE data with already existing normative data of TAPSE [2] (comparing 1.5 to 2.14 cm for 12 years of age, and 1.3 cm to 2.45 cm for 17 years of age). This might highlight the importance of their data for future pediatric PAH follow ups. We want to encourage the prospective use of echocardiography for routine assessment of RV systolic function in pediatric PAH patients.

    References 1.) Di Maria MV, Younoszai AK, Mertens L, Landeck BF 2nd, Ivy DD, Hunter KS, Friedberg MK. RV stroke work in children with pulmonary arterial hypertension: estimation based on invasive haemodynamic assessment and correlation with outcomes. Heart 2014 Apr 29. doi: 10.1136/heartjnl-2013- 305298 [Epub ahead of print].

    2.) Koestenberger M, Nagel B, Ravekes W, Avian A, Heinzl B, Fandl A, et al. Tricuspid annular peak systolic velocity (S') in children and young adults with pulmonary artery hypertension secondary to congenital heart diseases, and in those with repaired tetralogy of Fallot: echocardiography and MRI data. J Am Soc Echocardiogr 2012; 25: 1041-9.

    Conflict of Interest:

    None declared

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  5. Female sex as a determinant of prehospital 12-lead ECG in ST elevation and non-ST elevation myocardial infarction patients

    To the editor: We read the article by Quinn et al1on the effects of prehospital 12-lead ECG (PHECG) on processes of care and mortality with great interest. The authors conclude that when a PHECG was used, patients with ST-elevation myocardial infarction and non-ST elevation myocardial infarction had better survival compared to those without. Interestingly, among the determinants associated with PHECG use, the authors identify female patients to be less likely to have a PHECG than male patients.

    When the authors discuss possible explanations to the sex differences in PHECG use, they suggest that the predominately male emergency medical services workers might be reluctant to perform a PHECG on female patients because of the need for intimate exposure. Furthermore female patients might also be less willing to agree to a PHECG compared to men. We argue that a more plausible explanation is uncontrolled confounding of presenting symptoms and type of myocardial infarction.

    When we analysed a similar ST-elevation myocardial infarction and non -ST elevation myocardial infarction population in the Swedish comprehensive SWEDEHEART2 register we found an odds ratio for women vs. men to receive a PHECG comparable to that in the article by Quinn et al: (SWEDEHEART: OR=0.89; 95 % CI 0.87-0.92) vs. (Quinn et al: OR=0.87; 95% CI 0.86-0.89). In Sweden 64% of the ambulance specialist nurses were male (The National Board of Health and Welfare).

    In accordance with previous findings3 we found women to report chest pain as their presenting symptom in a lesser degree than men, 77.5% vs. 84.8%. Patients with atypical MI symptoms (e.g. no chest pain) are less likely to receive a PHECG compared to patients with chest pain, in SWEDEHEART 12.6% vs. 35.1%. When stratifying according to presenting symptoms, the sex differences almost disappeared, table 1. In addition non -ST elevation myocardial infarction patients are less likely to receive a PHECG compared to ST-elevation myocardial infarction patients, in SWEDEHEART 23.4% vs. 46.4%. Non-ST elevation myocardial infarction occurs more frequently than ST-elevation myocardial infarction in female patients, in SWEDEHEART 38.0% vs. 33.6%. Similarly in the Myocardial Ischaemia National Audit Project (MINARP) cohort4 which Quinn et al analysed. After stratification of presenting symptom and myocardial infarction type, the sex differences completely disappeared.

    We believe that if Quinn et al controls for presenting symptom and myocardial infarction type, the difference in PHECG use among men and women will disappear.

    Kristina Klerdal1 Christoph Varenhorst2 Stefan James2 Lars Alfredsson1 Hans Blomberg3 Tahereh Moradi1,4

    1Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Sweden

    2Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden

    3Department of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden

    4Centre for Epidemiology and Social Medicine, Health Care Services, Stockholm County Council, Sweden

    Contributors TM acquisition of data. KK conceived the letter, analysed the data and wrote the first draft. CV, SJ, LA, HB and TM contributed with editing of the content and specifics of the letter. All authors reviewed and approved the final product.

    Correspondence to MSc Kristina Klerdal, Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden; Kristina.Klerdal@ki.se

    Competing interest None

    REFERENCES 1 Quinn T, Johnsen S, Gale CP, et al. Effects of prehospital 12-lead ECG on processes of care and mortality in acute coronary syndrome: a linked cohort study from the Myocardial Ischaemia National Audit Project. Heart 2014;100:944-50. 2 Jernberg T, Attebring MF, Hambraeus K, et al. The Swedish Web-system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies (SWEDEHEART). Heart 2010;96:1617-21. 3 Coventry LL, Finn J, Bremner AP. Sex differences in symptom presentation in acute myocardial infarction: a systematic review and meta- analysis. Heart Lung 2011;40:477-91. 4 Gale CP, Cattle BA, Woolston A, et al. Resolving inequalities in care? Reduced mortality in the elderly after acute coronary syndromes. The Myocardial Ischaemia National Audit Project 2003-2010. Eur Heart J. 2012;33:630-9.

    ? Table 1 Prehospital 12-lead electrocardiogram (PHECG) use and sex in patients who came via emergency medical services

    Overall PHECG No PHECG OR estimate 95% CI

    women vs. men All patients (n)

    81,190 25,210 55,980

    Female

    36.5% 34.8% 37.3% 0.89 0.87 to 0.92

    Patients chest pain* (n)

    66,695 23,389 43,306

    Female

    34.5% 34.0% 34.7% 0.97 0.94 to 1.00

    STEMI

    24,450 12,062 12,388

    Female

    32.4% 32.3% 32.4% 0.99 0.94 to 1.05

    NSTEMI

    42,245 11,327 30,918

    Female

    35.7% 35.8% 35.7% 1.01 0.96 to 1.05

    Patients atypical symptoms* (n)

    11,799 1,487 10,312

    Female

    45.9% 45.1% 46.0% 0.96 0.86 to 1.08

    STEMI

    2,030 363 1,667

    Female

    46.3% 43.0% 47.0% 0.85 0.68 to 1.07

    NSTEMI

    9,769 1,124 8,645

    Female

    45.9% 45.8% 45.9% 1.00 0.88 to 1.13

    STEMI, ST-elevation myocardial infarction; NSTEMI, non ST-elevation myocardial infarction Crude odds ratios (OR) with 95% confidence intervals (CI) were calculated by logistic regression analysis. *Patients with missing information on presenting symptoms were deleted.

    Conflict of Interest:

    None declared

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  6. The BLOCK HF authors reply to the article: BLOCK HF: a game changer or a step too far?

    Dear Editor:

    In response to Dr. Witte's commentary, we want to provide additional information to allay some of his concerns. Our firm opinion is that BLOCK HF will indeed benefit the patient population included in the trial.

    In his editorial, Dr. Witte states that many patients enrolled in BLOCK HF were likely indicated for cardiac resynchronization therapy (CRT) even before enrollment in the trial. On the contrary, patients who were indicated for CRT were excluded from the trial. Indications for CRT did change over the duration of the trial, but at the time of enrollment, the trial excluded patients who had contemporaneous indications for CRT. Importantly, only 2.5% of the patients randomized as of the end of 2013 had met a contemporaneous CRT indication, while at least 15% of randomized BLOCK HF patients progressed to a CRT indication within 12 months of enrollment, because of progression of heart failure and ventricular dyssynchrony.

    Secondly, Witte points out that the study lacked a strong control group, since all patients received a biventricular (BiV) device. One of the strengths of the trial was the design. The trial could not have been a double-blinded trial (thereby avoiding placebo effects) without implanting all patients with CRT. All subjects had a pacing indication and thereby would have undergone implantation of a pacing device had they not been in the trial, unlike some CRT trials in the past such as COMPANION (1) or CARE-HF. (2) Thus, the incremental risk of implanting the left ventricular (LV) lead, which was turned OFF unless the subject was randomized to the BiV arm, was the difference between what the Control arm subjects received and what they would have received had they not been in the trial. However, designing the trial this way did make it easier for subjects in the Control arm to cross over to the BiV therapy arm, which could have resulted in a reduced treatment effect in the trial.

    The MOST (3) substudy showed that the risk of a heart failure hospitalization increased progressively up to 40% ventricular pacing. In order for patients to be included in BLOCK HF, atrioventricular (AV) block had to be documented in their medical history or they had to fail to conduct 1:1 during atrial pacing at 100 beats/min prior to device implantation. Thus, patients in BLOCK HF required ventricular pacing the great majority of the time, indicating that protocols to minimize ventricular pacing would not be effective. Additionally, a subgroup analysis of the varying degrees of AV block yielded a consistent effect on the primary outcome in favor of BiV pacing. (4) While Dr. Witte suggests that further analysis is needed in subgroups, the primary endpoint results were consistent across all subgroups.

    We agree that, in patients who have adequate AV conduction, minimizing ventricular pacing is preferred. Pacemakers and ICDs with ventricular pacing reduction therapies have been available since 2004, and thus during the majority of the enrollment period of BLOCK HF, but trials that studied the efficacy of these algorithms excluded AV block patients. If a clinician believes that an AV block subject's ventricular pacing percentage can be reduced below 40%, it is possible that a pacemaker or ICD with ventricular pacing reduction algorithms may be just as effective, but there are currently not data available to support this.

    Finally, from a cost-benefit view, the study showed that 18% of patients met a current CRT indication within one year. The REPLACE study showed that the risk of infection and other complications during system upgrades is nearly 19%, more than four times that of standard replacements. LV lead-related complications occurred in 6.3% of study patients (and not 10% as Dr. Witte states - the 10% figure is for procedure or CRT system-related complications within 30 days). Additionally, one could argue that the adverse events associated with LV lead complications such as dislodgement are likely less detrimental ultimately to a patient than those associated with heart failure hospitalizations. BLOCK HF data suggested that the two- year mortality risk increases from 8.8% to 41% after the first heart failure hospitalization, and the trial suggested that implanting these patients with CRT reduces this risk.

    Anne B. Curtis, MD University at Buffalo Buffalo, NY

    References:

    Bristow MR, et al. Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION). Cardiac-Resynchronization Therapy with or without an Implantable Defibrillator in Advanced Chronic Heart Failure. N Engl J Med 2004; 350:2140-2150

    2 Cleland JG, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005 Apr 14; 352(15):1539-49.

    3 Sweeney MO, et al. Effect of pacing mode and cumulative percent time ventricular paced on heart failure in patients with sick sinus syndrome and baseline QRS duration less than 120 milliseconds in MOST. PACE. 2002; 24:690.

    4 Curtis AB. Editorial response to Biventricular Pacing for Atrioventricular Block and Systolic Dysfunction. N Engl J Med 2013; 369:578-579. August 8, 2013.

    Conflict of Interest:

    Dr. Curtis has received honoraria from Medtronic, Inc. for consulting and speaking engagements, and also serves on an advisory board for St. Jude Medical and has received honoraria for speaking.

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  7. Comments on: The infective endocarditis team: recommendations from an international working group

    Chambers et al1 give some wise recommendations regarding infective endocarditis management. They recognize the grim prognosis of the disease (mortality: 20-64%), the importance of dedicated teams of experts, and the prominent role of early surgery; despite this, they suggest that some patients can be adequately managed in centres without dedicated teams of experts and surgical facilities, and propose nine indications for transfer patients to a surgical centre. To our opinion, every patient with infective endocarditis should be evaluated and treated in centres with dedicated experts and surgical facilities for several reasons: 1) severe complications may appear at any time and may require urgent diagnosis and treatment by experts; moreover, transferring a patient with septic shock or acute pulmonary oedema contributes to more clinical and haemodynamic instability; 2) an abscess, one of the indications proposed for transferring, and other periannular complications, may be missed by non- experts in imaging; 3) failure to respond to antibiotics is defined in the guidelines as the persistence of positive blood cultures 7-10 days after the initiation of antibiotic therapy2 but this arbitrary cut-off point may be too late3; 3) emboli can be silent or with subtle symptoms and can be easily missed even by experts; 4) severe regurgitation in the context of a valve with important tissue damage can be difficult to assess. Our experience is in agreement with this concept. We used to recommend that patients could stay at their hospital if no high-risk markers were present; eventually, some of those patients were transferred to our centre with poorer clinical condition. Infective endocarditis is the cardiac disease with the highest rate of death, much higher than acute myocardial infarction and many types of cancer, which needs a combined medico- surgical therapeutic approach, which should be undertaken at medico- surgical centres.

    1. Chambers J, Sandoe J, Ray S, et al. The infective endocarditis team: recommendations from an international working group. Heart 2014; 100: 524-527.

    2. Habib G, Hoen B, Tornos P, et al. Guidelines on the prevention, diagnosis, and treatment of infective endocarditis of the European Society of Cardiology. Eur Heart J 2009; 30: 2369-2413.

    3. Lopez J, Sevilla T, Vilacosta I, et al. Prognostic role of persistent positive blood cultures after initiation of antibiotic therapy in left-sided infective endocarditis. Eur Heart J 2013; 34: 1749-54.

    Conflict of Interest:

    None declared

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  8. INSIGHTS INTO INTRADIALYTIC ATRIAL FIBRILLATION ONSET MECHANISMS

    It is with interest that we read the paper by Buiten et al. (1) in which the authors, using the implantable cardioverter defibrillator (ICD) remote monitoring function in patients enrolled in the ICD-2 trial, showed that hemodialysis (HD) is a trigger for atrial fibrillation (AF) episodes. The study of Buiten confirms some observations we made in the recent past. Few years ago we studied, by high frequency electrocardiography, the effects of the HD session on P-wave duration (Pwd), an expression of intra -atrial conduction velocity, demonstrating that the procedure induced a prolongation of Pwd closely related to the reduction of the plasma potassium concentration. When the pre-and post-dialysis values of electrolytes were put in a computational model that simulates the atrial action potential, the atrial potential upstroke was slowed down from the beginning towards the end of the HD session. Also we observed a reduction of the effective refractory period (2). It is well known that both phenomena are part of the electrical remodeling at the base of AF onset. These data were also confirmed by a multiscale computer model (3). Buiten et al. show that a lower concentration of potassium in the dialysis bath (which usually is associated to a high shift of the electrolytes during the dialysis session) is associated with a higher probability of occurrence of AF episodes intra and peri-HD session. This observation is concordant with our data. Recently, we reported a case of a patient in whom HD session constantly induced episodes of paroxysmal AF. The episodes were preceded by a reduction of the plasma potassium levels and an increase of supraventricular ectopic beats and of the vagal component of heart rate variability as evaluated by spectral analysis. The computational model, feeded with the data of each session, consistently showed an increase in atrial potential upstroke duration and a reduction in the effective refractory period. Both phenomena were enhanced when the IK,ACh current, sensitive to acetylcholine, was added to the model, suggesting that the vagal rather than adrenergic stimulation plays an important role in the genesis of intradialytic AF episodes (4). We think that it would be very interesting to test this hypothesis using data obtained from the remote monitoring of ICD-2 trial patients.

    References 1. Buiten MS, de Bie MK, Rotmans BA et al. The dialysis procedure as a trigger for atrial fibrillation: new insights in the development of atrial fibrillation in dialysis patients. Heart 2014; 100: 685-690 2. Severi S, Pogliani D, Fantini G et al. Alterations of atrial electrophysiology induced by electrolyte variations: combined computational and P-wave analysis. Europace 2010; 12: 842-849 3. Krueger MW, Severi S, Genovesi S et al. Alterations of atrial electrophysiology related to hemodialysis session: insights from a multiscale computer model. J Electrocardiol 2011; 44: 176-183 4. Vincenti A, Passini E, Fabbrini P et al. Recurrent intradialytic paroxysmal atrial fibrillation: hypotheses on onset mechanisms based on clinical data and computational analysis. Europace 2014; 16:396-404

    Conflict of Interest:

    None declared

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  9. Decision to intervene in asymptomatic mitral regurgitation - "more art than science"

    In a recently published Editorial to the new 2014 ACC/AHA Guidelines for the Management of Patients with Valvular Heart Disease its authors note that "since in asymptomatic patients decisions on timing of intervention is made primarily on the basis of left ventricular size and function and quantitative evaluation of mitral regurgitation severity, accurate measurements of the left ventricular function, as well as the degree of MR, are essential."(1) This is now even more important than before because the guidelines consider surgery reasonable (class IIa indication) in the so called grade C1 asymptomatic severe mitral regurgitation with left ventricular ejection fraction of >60% and left ventricular end-systolic diameter of <40 mm. In such patients, as ventricular function is normal, the decision to intervene is based almost solely on the assessment of mitral regurgitation severity. Therefore, the guidelines emphasize "the need to assure quality control for a comprehensive imaging and Doppler echocardiogram, performed by experienced laboratories, with the ability to perform accurate and reproducible quantitative measurements of mitral regurgitation severity." However quantitative measurements are not routinely performed even in carefully selected tertiary referral centers, as evidenced by the results of the recently published results of the Mitral Regurgitation International Database (MIDA) registry, where the decisions to operate were made based solely on semiquantitative assessment of mitral regurgitation severity.(2) Although accepting only quantitative measurements of mitral regurgitation severity may seem to be the solution, Biner et al. (3) recently demonstrated that, in the group of experienced echocardiologists from academic institutions, interobserver agreement for quantitative methods for identifying severe from nonsevere mitral regurgitation was poor and actually similar to the qualitative assessment (and, as stated in the accompanying editorial, it was "more art than science"). (4) Therefore we should be aware that, especially in asymptomatic patients with normal left ventricular function, the probability of false positive diagnosis of severe mitral regurgitation, based on current echocardiographic grading, is not negligible. Therefore in such patients, with lower pre-test probability of severe valvular lesion, a conservative approach to the diagnosis of mitral regurgitation is always essential to decrease the risk of performing unnecessary surgery. References: 1) Nishimura RA, Otto C. 2014 ACC/AHA valve guidelines: earlier intervention for chronic mitral regurgitation. Heart. 2014 online doi: 10.1136/heartjnl-2014-305834. 2) Suri RM, Vanoverschelde JL, Grigioni F, et al. Association between early surgical intervention vs watchful waiting and outcomes for mitral regurgitation due to flail mitral valve leaflets. JAMA. 2013;310:609-16. 3) Biner S, Rafique A, Rafii F, Tolstrup K, Noorani O, Shiota T, Gurudevan S, Siegel RJ. Reproducibility of proximal isovelocity surface area, vena contracta, and regurgitant jet area for assessment of mitral regurgitation severity. JACC Cardiovasc Imaging. 2010;3:235-43. 4) Grayburn PA, Bhella P. Grading severity of mitral regurgitation by echocardiography: science or art? JACC Cardiovasc Imaging. 2010;3:244-6.

    Conflict of Interest:

    None declared

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  10. Statistical significance vs clinical importance

    The primary finding reported in this study [1] is a correlation coefficient of -0.042 between the inflammatory marker of interleukin IL-6 and the percentage flow-mediated dilation index (FMD%). The difference between this correlation coefficient and zero is statistically significant (P=0.02) for the large sample of participants that was studied (n=3404).

    Here we have a clear illustration of why it is important to distinguish between clinical and statistical significance in research. The coefficient of determination, calculated from the square of the reported correlation coefficient, is 0.0018. This means that less than 0.2% of the variability in FMD% is explained by the variability in IL-6.

    Weiner et al.[1] reported minimum correlations to achieve statistical significance for the various cohort sample sizes. Nevertheless, the minimum clinically important correlation coefficient was not reported, nor was a robust clinical anchor rationalised to interpret the findings properly. The appraisal of clinical significance is, nevertheless, straightforward in this study. The 95% confidence interval for a correlation of -0.042 with a sample size of 3404 is approximately -0.08 to -0.01. Even if the smallest worthwhile effect is as low as 0.1 ("small" by all definitions), then the true population correlation between IL-6 and FMD% is almost certainly trivial and not clinically important.

    We were initially interested in this study because of the size- scaling problems with the FMD% index, which were described recently, using examples from the same MESA dataset [2]. These scaling issues are also clearly evident in the study by Weiner et al.[1]. For example, the apparently higher FMD% reported for women is merely because baseline diameter (Dbase) is smaller in women, and because FMD% does not allometrically scale for Dbase properly - illustrated, consistently in the literature, by the negative correlation between FMD% and Dbase [2, 3, 4]. This latter correlation, which is mediated by statistical rather physiological mechanisms, tends to be between -0.8 and -0.4, and is, therefore, almost certainly clinically significant {2, 3, 4].

    References

    1. Weiner SD, Ahmed HN, Jin Z, et al. Heart Published Online First: 8th April, 2014. doi:10.1136/heartjnl-2013-304893.

    2. Atkinson G, Batterham AM. The percentage flow-mediated dilation index: A large-sample investigation of its appropriateness, potential for bias and causal nexus in vascular medicine. Vascular Medicine 2013;18: 354 -365.

    3. Atkinson G, Batterham AM. (2013b) Allometric scaling of diameter change in the original flow-mediated dilation protocol. Atherosclerosis 2013; 226:425-427.

    4. Atkinson G, Batterham AM, Thijssen DHJ, Green DJ. A new approach to improve the specificity of flow-mediated dilation for indicating endothelial function in cardiovascular research. J Hypertens 2013;31:287- 291.

    Conflict of Interest:

    None declared

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