Martínez –Milla el al, report an interesting case of cardiac lymphoma, presenting as complete AV block.
A close look at the electrocardiogram, reveals a P wave with a normal frontal axis, broad (duration > 120 ms), and bimodal ( notched). These are the diagnostic hallmarks of partial interatrial block (IAB).
In this patient, the lymphoma probably infiltrates the Bachmann’s bundle, interrupting the preferential pathway of left atrial activation, causing partial IAB.
Although often overlooked, IAB is frequent in the elderly, and it is associated with atrial arrhythmias and stroke.
Because the diagnosis of IAB relies on the morphology and duration of the P wave, a meticulous analysis of the electrocardiogram is mandatory.
The recommendation that combined antiplatelet and new oral anticoagulant(NOAC) therapy should rely on the lowest approved NOAC dose effective for stroke prevention(1) is one which favours low-dose edoxaban instead of either dabigatran, rivaroxaban, or apixaban, when reduction of risk of gastrointestinal(GIT) bleeding is taken into account. In a review of clinical experience of bleeding associated with NOACs(dabigatran, rivaroxaban, apixaban, and edoxaban) versus warfarin in nonvalvular atrial fibrillation(NVAF), edoxaban 30 mg/day was the only antithrombotic agent associated with significantly(p < 0.001) lower risk of GIT bleeding than warfarin(Hazard Ratio: 0.67;95% Confidence Interval 0.53 to 0.83). For apixaban and for dabigatran 110 mg BID, the risk of GIT bleeding was comparable with the risk associated with warfarin use. For rivaroxaban and for dabigatran 150 mg BID the risk of GIT haemorrhage was significantly higher(P < 0.0001, and p < 0.001, respectively) than the GIT bleeding risk associated with warfarin(2).
In a study where 92.2% of 5301 NVAF users of antiplatelet agents were prescribed a NOAC in combination with only one antiplatelet agent vs 86.3% of 9106 NVAF users of antiplatelet agents who were prescribed warfarin with only one antiplatelet agent , concomitant antiplatelet and NOAC use was associated with significantly lower risk of intracranial bleeding than concomitant antiplatelet and warfarin use(HR 0.68, 95% CI, 0.51 to 0.91). Ne...
The recommendation that combined antiplatelet and new oral anticoagulant(NOAC) therapy should rely on the lowest approved NOAC dose effective for stroke prevention(1) is one which favours low-dose edoxaban instead of either dabigatran, rivaroxaban, or apixaban, when reduction of risk of gastrointestinal(GIT) bleeding is taken into account. In a review of clinical experience of bleeding associated with NOACs(dabigatran, rivaroxaban, apixaban, and edoxaban) versus warfarin in nonvalvular atrial fibrillation(NVAF), edoxaban 30 mg/day was the only antithrombotic agent associated with significantly(p < 0.001) lower risk of GIT bleeding than warfarin(Hazard Ratio: 0.67;95% Confidence Interval 0.53 to 0.83). For apixaban and for dabigatran 110 mg BID, the risk of GIT bleeding was comparable with the risk associated with warfarin use. For rivaroxaban and for dabigatran 150 mg BID the risk of GIT haemorrhage was significantly higher(P < 0.0001, and p < 0.001, respectively) than the GIT bleeding risk associated with warfarin(2).
In a study where 92.2% of 5301 NVAF users of antiplatelet agents were prescribed a NOAC in combination with only one antiplatelet agent vs 86.3% of 9106 NVAF users of antiplatelet agents who were prescribed warfarin with only one antiplatelet agent , concomitant antiplatelet and NOAC use was associated with significantly lower risk of intracranial bleeding than concomitant antiplatelet and warfarin use(HR 0.68, 95% CI, 0.51 to 0.91). Nevertheless, risk of GIT bleeding was comparable(HR 1,08, 95% CI, 0.81 to 1.45)(3).
Given the fact that VKA therapy is associated with greater risk of intracranial bleeding than NOAC therapy, not only in the absence of concomitant antiplatelet drug use(2), but also in the context of combined anticoagulant and only one antiplatelet agent (3), the safest use of triple antithrombotic therapy(TAT) appears to be one which involves either low-dose edoxaban, low-dose dabigatran or apixaban so as to optimise mitigation of the risk of gastrointestinal bleeding..
Although PIONEER AF-PCI was a TAT study which documented significantly(p < 0.001) lower rates of clinically significant bleeding in recipients of TAT involving low dose rivaroxaban than in recipients of TA involving warfarin that study was not powered to evaluate non inferiority of the low-dose rivaroxaban regime to the warfarin regime for thromboprophylaxis against NVAF-related stroke(4). Future trials should now optimise the advantage that the sole use of low-dose edoxaban enjoys over sole use of other NOACs in mitigating the risk of both intracranial and GIT bleeding, by exploring the possibility that the universal inclusion of the 30 mg/day edoxaban dose (irrespective of renal function and body weight), in a TAT regime might be non inferior to a TAT regime that involves warfarin, with regard to thromboprophylaxis against NVAF-related stroke. .
I have no funding and no conflict of interest
References
(1) Capodano D
Triple antithrombotic therapy after ACS and PCI in patients on chronic oral anticoagulation Update
Heart 2018;104:1976-1983
(2) Eikelboom J., Meril G
Bleeding with direct oral anticoagulants vs warfarin: Clinical experience
Am J Med 2016;129:S33-S40
(3)Douros A., Renoux X., Yin H et al
Concomitant use of direct oral anticoagulants with antiplatelet agents and the risk of major bleeding in patients with nonvalvular atrial fibrillation
Am J Med 2018;DOI.org/10.1016/amjmed 2018.10.008
(4) Gibson CM., Mehran R., Bode C et al
Prevention of bleeding in patients with atrial fibrillation undergoing PCI
N Engl J Med 2016;375:2423-2434
We read with interest the article by Rusingiza et al (1)and report our experience from Northern Sri Lanka, a Low Middle Income Country (LMIC). Sri Lanka had invested heavily in free education and healthcare with demonstrably high literacy rates and positive health indices (2). However, the focus of the healthcare related investment has been in the secondary and tertiary care institutions, whilst primary care systems remain poorly developed. Northern Sri Lanka had been further impacted adversely by three decades of civil strife.
We report our experience in the management of post-valvular surgery patients at the Jaffna Teaching Hospital, the only tertiary referral centre for the region. Improvements in socioeconomic conditions has resulted in a decline in the incidence of rheumatic heart disease in Sri Lanka which accounted for only 0.34% of all deaths in 2017 (3). Concurrently, established patients receiving prosthetic heart valves has increased mainly due to improving access to surgical facilities. Unfortunately, Northern Sri Lanka had been without facilities for cardiac surgery for three decades leaving patients to access facilities elsewhere in the country. Post-surgery follow-up occurred primarily in Jaffna and a few other secondary care hospitals in the region. Unlike in the Rwandan study, most of our patients received parenteral penicillin prophylaxis thereby enhancing compliance and were fitted with metallic rather than bioprosthetic valves, thereby necessitat...
We read with interest the article by Rusingiza et al (1)and report our experience from Northern Sri Lanka, a Low Middle Income Country (LMIC). Sri Lanka had invested heavily in free education and healthcare with demonstrably high literacy rates and positive health indices (2). However, the focus of the healthcare related investment has been in the secondary and tertiary care institutions, whilst primary care systems remain poorly developed. Northern Sri Lanka had been further impacted adversely by three decades of civil strife.
We report our experience in the management of post-valvular surgery patients at the Jaffna Teaching Hospital, the only tertiary referral centre for the region. Improvements in socioeconomic conditions has resulted in a decline in the incidence of rheumatic heart disease in Sri Lanka which accounted for only 0.34% of all deaths in 2017 (3). Concurrently, established patients receiving prosthetic heart valves has increased mainly due to improving access to surgical facilities. Unfortunately, Northern Sri Lanka had been without facilities for cardiac surgery for three decades leaving patients to access facilities elsewhere in the country. Post-surgery follow-up occurred primarily in Jaffna and a few other secondary care hospitals in the region. Unlike in the Rwandan study, most of our patients received parenteral penicillin prophylaxis thereby enhancing compliance and were fitted with metallic rather than bioprosthetic valves, thereby necessitating the need for long-term monitoring on warfarin, the only available anticoagulant in the state sector in Sri Lanka. This need, together with the increase in valvular surgery following the recent development of cardiac surgery in Jaffna, further emphasizes the urgent need for managing these patients in integrated primary care setups closer to their homes.
It is encouraging that Sri Lanka has now recognized the urgency to develop the primary care infrastructure, driven by the emerging epidemic in Non-Communicable Diseases. The lesson from Rwanda is of relevance to countries like Sri Lanka and will decrease the overloading of secondary and tertiary institutions with overall reductions in the cost of healthcare.
References:
1. Rusingiza EK, El-Khatib Z, Hedt-Gauthier B et al. Outcomes for patients with rheumatic heart disease after cardiac surgery followed at rural district hospitals in Rwanda. Heart. 2018; 104:1707-1714
2. WHOAnnualReport2012.http://www.who.int/kobe_centre/publications/annual_report2012_en.pdf.
3. https://www.worldlifeexpectancy.com/sri-lanka-rheumatic-heart-disease
There was significantly higher usage of both loop diuretics and aldosterone antagonist in the group with persistent hyponatraemia. Is it possible that one of the clinical manifestation of RV dysfunction, i.e peripheral oedema, led to an increased use of diuretic in this group and hence hyponatraemia as a complication of this treatment? Over diuresis in this scenario leads to activation of the RAAS which in turn worsens pulmonary hypertension and tricuspid regurgitation. The consequence of this is worsening peripheral oedema and the tendency to increase the diuretic dose.Hyponatraemia therefore may not be an independent predictor of outcome as stated.
We read with great interest the article by Elias et al (1) regarding the longer term clinical outcomes from the EXPLORE trial. The authors are to be congratulated for conducting this important study to address the optimal management of patients presenting with a concurrent CTO in a non-infarct related artery (non-IRA) during a STEMI. The results at 1 year are similar to those in the initial 4 month outcome (2), with no difference in the primary endpoints of cardiac MRI determined LVEF or LVEDV in either CTO-PCI and CTO-No PCI groups. At a median of 3.9 years, there was no difference in long term MACE, although an apparent increase in cardiovascular mortality (6% vs 1%, p=0.02).
Whilst this important study adds to the much needed literature on randomised studies related to PCI of CTOs, the results should be interpreted with caution. Firstly, large scale contemporaneous studies in CTO PCI have had procedural success rates in the region of 90% (3), whilst in EXPLORE (2) this rate was considerably lower, at 73% by core laboratory. This suggests either a more anatomically complex subset of patients, or else attempts by non-dedicated CTO PCI operators, both of which affect the interpretation of the intention to treat population.
Furthermore, the mortality data should be reviewed with care. At 12 months, there were 4 cardiovascular deaths (2.7%) in the CTO PCI group, with no deaths in the CTO-No PCI groups. These rates are significantly lower compared with other t...
We read with great interest the article by Elias et al (1) regarding the longer term clinical outcomes from the EXPLORE trial. The authors are to be congratulated for conducting this important study to address the optimal management of patients presenting with a concurrent CTO in a non-infarct related artery (non-IRA) during a STEMI. The results at 1 year are similar to those in the initial 4 month outcome (2), with no difference in the primary endpoints of cardiac MRI determined LVEF or LVEDV in either CTO-PCI and CTO-No PCI groups. At a median of 3.9 years, there was no difference in long term MACE, although an apparent increase in cardiovascular mortality (6% vs 1%, p=0.02).
Whilst this important study adds to the much needed literature on randomised studies related to PCI of CTOs, the results should be interpreted with caution. Firstly, large scale contemporaneous studies in CTO PCI have had procedural success rates in the region of 90% (3), whilst in EXPLORE (2) this rate was considerably lower, at 73% by core laboratory. This suggests either a more anatomically complex subset of patients, or else attempts by non-dedicated CTO PCI operators, both of which affect the interpretation of the intention to treat population.
Furthermore, the mortality data should be reviewed with care. At 12 months, there were 4 cardiovascular deaths (2.7%) in the CTO PCI group, with no deaths in the CTO-No PCI groups. These rates are significantly lower compared with other trials in the modern era of primary-PCI for STEMI, such as TOTAL (4) (3.7% 12 month cardiovascular mortality in 10,064 patients and 10.8% in patients with concurrent CTO in non-IRA) and HORIZONS-AMI (5) (2.9% 12 month mortality in 3,602 patients). This lower than expected event rate may affect the ability to detect differences between treatment arms. Furthermore, the mechanism of the deaths in the CTO-PCI group at 12 months was stent thrombosis (ST) in all 4 cases. Whilst drug eluting stents were used for all CTO-PCI and the majority of culprit STEMI lesions, along with mandated dual antiplatelet therapy for all patients, the overall rate of probable or definite ST was relatively high at 5.6%, in contrast to TOTAL4 and HORIZONS-AMI5, which had a 1.9% and 3% ST rate at 12 months. Given the CTO PCI procedure was conducted at operator discretion it would be interesting to note whether intravascular imaging was used, as IVUS guided CTO PCI has been shown to reduce rates of ST. Clarification on this would be important, and may help to explain the high rate of ST.
24.0% of patients in the CTO-No PCI group underwent either CTO PCI or CABG within 1 year. Clearly this high cross over rate has implications for data analysis, and further underlines the inherent issues with attempting to conduct a meaningful CTO PCI trial. Finally, this study was addressing the issue of early complete revascularisation in patients with a STEMI and concurrent CTO. We have previously shown (6) with landmark analysis, that even beyond 1 month, the presence of a CTO in patients with a STEMI is associated with significantly poorer prognosis above and beyond that of multi-vessel disease. Clearly, the “double jeopardy” with a CTO of a non-infarct related artery and STEMI results in a greater territory of ischaemic myocardium with an early rate of cardiogenic shock and mortality. However, whether a staged PCI procedure after allowing recovery of the myocardium would result in improved outcomes should be an area of ongoing research.
References
1. Elias J, van Dongen IM, Ramunddal T, Laanmets P, Eriksen E, Meuwissen M, Michels HR, Bax M, Ioanes D, Suttorp MJ, Strauss BH, Barbato E, Marques KM, Claessen B, Hirsch A, van der Schaaf RJ, Tijssen JGP, Henriques JPS, Hoebers LP and investigators E. Long-term impact of chronic total occlusion recanalisation in patients with ST-elevation myocardial infarction. Heart. 2018;104:1432-1438.
2. Henriques JP, Hoebers LP, Ramunddal T, Laanmets P, Eriksen E, Bax M, Ioanes D, Suttorp MJ, Strauss BH, Barbato E, Nijveldt R, van Rossum AC, Marques KM, Elias J, van Dongen IM, Claessen BE, Tijssen JG, van der Schaaf RJ and Investigators ET. Percutaneous Intervention for Concurrent Chronic Total Occlusions in Patients With STEMI: The EXPLORE Trial. J Am Coll Cardiol. 2016;68:1622-1632.
3. Park S-J. DECISION-CTO: Optimal Medical Therapy With or Without Stenting For Coronary Chronic Total Occlusion. American College of Cardiology Annual Scientific Session (ACC 2017). 2017.
4. Jolly SS, Cairns JA, Yusuf S, Rokoss MJ, Gao P, Meeks B, Kedev S, Stankovic G, Moreno R, Gershlick A, Chowdhary S, Lavi S, Niemela K, Bernat I, Cantor WJ, Cheema AN, Steg PG, Welsh RC, Sheth T, Bertrand OF, Avezum A, Bhindi R, Natarajan MK, Horak D, Leung RC, Kassam S, Rao SV, El-Omar M, Mehta SR, Velianou JL, Pancholy S, Dzavik V and Investigators T. Outcomes after thrombus aspiration for ST elevation myocardial infarction: 1-year follow-up of the prospective randomised TOTAL trial. Lancet. 2016;387:127-35.
5. Mehran R, Lansky AJ, Witzenbichler B, Guagliumi G, Peruga JZ, Brodie BR, Dudek D, Kornowski R, Hartmann F, Gersh BJ, Pocock SJ, Wong SC, Nikolsky E, Gambone L, Vandertie L, Parise H, Dangas GD, Stone GW and Investigators H-AT. Bivalirudin in patients undergoing primary angioplasty for acute myocardial infarction (HORIZONS-AMI): 1-year results of a randomised controlled trial. Lancet. 2009;374:1149-59.
6. Allahwala UK, Jolly SS, Dzavik V, Cairns JA, Kedev S, Balasubramanian K, Stankovic G, Moreno R, Valettas N, Bertrand O, Lavi S, Velianou JL, Sheth T, Meeks B, Brilakis ES and Bhindi R. The Presence of a CTO in a Non-Infarct-Related Artery During a STEMI Treated With Contemporary Primary PCI Is Associated With Increased Rates of Early and Late Cardiovascular Morbidity and Mortality: The CTO-TOTAL Substudy. JACC Cardiovasc Interv. 2018;11:709-711.
I read with great interest the paper by Elias et al regarding the mid-term and long-term clinical outcome of the Evaluating Xience and left ventricular function in Percutaneous Coronary Interventions on occlusiOns afteR ST elevation myocardial infarction (EXPLORE) trial. [1] The authors are to be congratulated for this detailed analysis evaluating the effect of chronic total occlusions – percutaneous coronary intervention (CTO-PCI) compared with CTO-No PCI on clinical outcome, left ventricular function and angina status in patients with ST elevation myocardial infarction (STEMI) with a concurrent CTO. The message of their study is that early CTO-PCI in patients with STEMI presenting with a concurrent CTO during primary PCI should not be performed routinely.
The authors also analysed the study population combined and found higher long-term mortality in patients who were older (>60 years) (11% vs 3%; HR 3.74; 95% CI 1.37 to 10.21; P=0.01), who had diabetes (15% vs 6%; HR 2.94; 95% CI 1.19 to 7.30; P=0.02), had a higher left ventricular enddiastolic volume at baseline (12% vs 1%; HR 13.04; 95% CI 1.70 to 100.30; P=0.01) and who had a high SYNTAX score (10% vs 4%; HR 2.50; 95% CI 1.01 to 6.20; P=0.048). They also stated that cardiac death was more frequent in the CTO-PCI arm (6.0% vs 1.0%, P=0.02) with no difference in all-cause mortality. However, it is known that a major prognostic factor in STEMI patients with a concurrent CTO is the presence of collateral feeding...
I read with great interest the paper by Elias et al regarding the mid-term and long-term clinical outcome of the Evaluating Xience and left ventricular function in Percutaneous Coronary Interventions on occlusiOns afteR ST elevation myocardial infarction (EXPLORE) trial. [1] The authors are to be congratulated for this detailed analysis evaluating the effect of chronic total occlusions – percutaneous coronary intervention (CTO-PCI) compared with CTO-No PCI on clinical outcome, left ventricular function and angina status in patients with ST elevation myocardial infarction (STEMI) with a concurrent CTO. The message of their study is that early CTO-PCI in patients with STEMI presenting with a concurrent CTO during primary PCI should not be performed routinely.
The authors also analysed the study population combined and found higher long-term mortality in patients who were older (>60 years) (11% vs 3%; HR 3.74; 95% CI 1.37 to 10.21; P=0.01), who had diabetes (15% vs 6%; HR 2.94; 95% CI 1.19 to 7.30; P=0.02), had a higher left ventricular enddiastolic volume at baseline (12% vs 1%; HR 13.04; 95% CI 1.70 to 100.30; P=0.01) and who had a high SYNTAX score (10% vs 4%; HR 2.50; 95% CI 1.01 to 6.20; P=0.048). They also stated that cardiac death was more frequent in the CTO-PCI arm (6.0% vs 1.0%, P=0.02) with no difference in all-cause mortality. However, it is known that a major prognostic factor in STEMI patients with a concurrent CTO is the presence of collateral feeding donor arteries from an infarct-related artery (IRA). Of patients with CTO, those with collateral flow from the IRA have significantly higher mortality than the non-IRA group (at 30 days: 52.2% vs. 10.9%, P<0.0001).[2] Obviously, in acute phase of these unstable conditions, the myocardium in the “remote” zone of infarction (CTO-zone) also ceases to contract. It is uncertain whether primary angioplasty in the IRA led to recover in the contractile function in the CTO zone. It would be very helpful if Elias et al could provide additional angiographic data regarding the IRA and the donor artery of CTO in their population (and the impact of PCI-CTO in this group). Surprisingly, in most post-myocardial infarction PCI-CTO studies relevant data are lacking.
1. Elias J, van Dongen IM, Råmunddal T, Laanmets P, et al. Long-term impact of chronic total occlusion recanalisation in patients with ST-elevation myocardial infarction. Heart. 2018 Feb 20. pii: heartjnl-2017-312698. doi: 10.1136/heartjnl-2017-312698. [Epub ahead of print]
2. Fujii T, Sakai K, Nakano M, et al. Impact of the origin of the collateral feeding donor artery on short-term mortality in ST-elevation myocardial infarction with comorbid chronic total occlusion. Int J Cardiol. 2016;218:158-163.
We thank dr. Katsouras for his response to our long-term EXPLORE manuscript (1). We agree that in the ST-segment elevation (STEMI) population the presence of collaterals to the concurrent chronic total occlusion (CTO) is of prognostic relevance. We previously reported in 413 consecutive STEMI patients with a CTO that the presence of well-developed collaterals to the CTO compared to poorly developed collaterals was associated with improved outcome. We also assessed the influence of the collateral origin on survival, as collaterals coming distally from the culprit lesion are (partially) blocked during the acute phase of STEMI. In 16% of the patients the collaterals originated directly or distal from the culprit lesion and these patients had a lower survival compared to the patients in whom the collaterals were not blocked during STEMI (2).
In the EXPLORE trial patients with well-developed collaterals to the CTO had a significantly better left ventricular (LV) function at 4 months follow-up. Nonetheless, we did not find a significant treatment effect of CTO-PCI on global LV function nor on clinical outcome in patients with poorly developed nor with well-developed collaterals (3). On a regional level we found that the recovery of segmental wall thickening of the dysfunctional CTO myocardium was better in patients with well-developed collaterals. However, no significant interaction of collateral quality on the effect of CTO PCI was found (4). In EXPLORE there were 34 p...
We thank dr. Katsouras for his response to our long-term EXPLORE manuscript (1). We agree that in the ST-segment elevation (STEMI) population the presence of collaterals to the concurrent chronic total occlusion (CTO) is of prognostic relevance. We previously reported in 413 consecutive STEMI patients with a CTO that the presence of well-developed collaterals to the CTO compared to poorly developed collaterals was associated with improved outcome. We also assessed the influence of the collateral origin on survival, as collaterals coming distally from the culprit lesion are (partially) blocked during the acute phase of STEMI. In 16% of the patients the collaterals originated directly or distal from the culprit lesion and these patients had a lower survival compared to the patients in whom the collaterals were not blocked during STEMI (2).
In the EXPLORE trial patients with well-developed collaterals to the CTO had a significantly better left ventricular (LV) function at 4 months follow-up. Nonetheless, we did not find a significant treatment effect of CTO-PCI on global LV function nor on clinical outcome in patients with poorly developed nor with well-developed collaterals (3). On a regional level we found that the recovery of segmental wall thickening of the dysfunctional CTO myocardium was better in patients with well-developed collaterals. However, no significant interaction of collateral quality on the effect of CTO PCI was found (4). In EXPLORE there were 34 patients (11%) with no visible collaterals or collaterals originating from the IRA occluded during STEMI. These patients had a significantly lower LVEF (38% versus 45%, p=0.001) and a higher LVEDV (226ml versus 213ml, p=0.37) at 4 months follow-up. Long-term MACE rates were also numerically higher in this group (20% versus 12%, Log-rank p=0.21). Mortality rates were not different between both groups (9.4% versus 9.3%, Log-rank p=0.40). We did not find an effect of CTO-PCI on LV function nor on clinical outcome in the patients with collaterals blocked during STEMI nor in patients with present collaterals.
Therefore, data regarding the value of the collateral circulation are conflicting and their exact role remains controversial. Further CTO research should focus more on the collateral circulation to determine whether collaterals should be of influence on treatment strategies or whether they are just unmodifiable markers of prognosis in these complex patients.
References:
1. Elias J, van Dongen IM, Ramunddal T, et al. Long-term impact of chronic total occlusion recanalisation in patients with ST-elevation myocardial infarction. Heart 2018 doi: 10.1136/heartjnl-2017-312698
2. Elias J, Hoebers LPC, van Dongen IM, et al. Impact of Collateral Circulation on Survival in ST-Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention With a Concomitant Chronic Total Occlusion. JACC Cardiovasc Interv 2017;10(9):906-14. doi: 10.1016/j.jcin.2017.01.026
3. Van Dongen IM, Elias J, Van Houwelingen KG, et al. P5156Impact of collateral filling on LVF and survival in STEMI patients with a concomitant CTO. An explorative subanalysis of the EXPLORE trial. European Heart Journal 2017;38(suppl_1):ehx493.P5156-ehx493.P56. doi: 10.1093/eurheartj/ehx493.P5156
4. Elias J, van Dongen IM, Hoebers LP, et al. Improved recovery of regional left ventricular function after PCI of chronic total occlusion in STEMI patients: a cardiovascular magnetic resonance study of the randomized controlled EXPLORE trial. J Cardiovasc Magn Reson 2017;19(1):53. doi: 10.1186/s12968-017-0369-z
We read with interest the excellent and timely article on increasingly detected cases of isolated tricuspid valve regurgitation (1) . The authors rightly note that there is an emerging population of adult patients without left-sided heart disease, pulmonary hypertension or congenital abnormalities who develop symptomatic isolated tricuspid regurgitation. While this is true, we believe that a proportion of these cases of isolated tricuspid regurgitation may well be congenital in origin.
The spectrum of congenital abnormalities of tricuspid valve abnormalities is large (2), and while Ebstein anomaly and tricuspid valve anomalies associated with atrioventricular septal defects and pulmonary atresia are the most commonly discussed, there is a group of patients with tricuspid valve dysplasia or congenitally abnormal tricuspid valves that are under-recognized. Said et al (3) and Dearani et al (4) from the authors’ institution have previously discussed the wide spectrum of congenital tricuspid valve anomalies. The importance of recognizing this group of cases as a separate entity is twofold. One that tricuspid valve dysplasia from failure of delamination of the tricuspid valve, like Ebstein anomaly can be associated with cardiomyopathy and arrhythmia and other congenital anomalies can be missed if focus if just on the valve. Secondly, surgical approach for tricuspid valve surgery, as authors suggest, should focus on the mechanisms of tricuspid regurgitation, which are uni...
We read with interest the excellent and timely article on increasingly detected cases of isolated tricuspid valve regurgitation (1) . The authors rightly note that there is an emerging population of adult patients without left-sided heart disease, pulmonary hypertension or congenital abnormalities who develop symptomatic isolated tricuspid regurgitation. While this is true, we believe that a proportion of these cases of isolated tricuspid regurgitation may well be congenital in origin.
The spectrum of congenital abnormalities of tricuspid valve abnormalities is large (2), and while Ebstein anomaly and tricuspid valve anomalies associated with atrioventricular septal defects and pulmonary atresia are the most commonly discussed, there is a group of patients with tricuspid valve dysplasia or congenitally abnormal tricuspid valves that are under-recognized. Said et al (3) and Dearani et al (4) from the authors’ institution have previously discussed the wide spectrum of congenital tricuspid valve anomalies. The importance of recognizing this group of cases as a separate entity is twofold. One that tricuspid valve dysplasia from failure of delamination of the tricuspid valve, like Ebstein anomaly can be associated with cardiomyopathy and arrhythmia and other congenital anomalies can be missed if focus if just on the valve. Secondly, surgical approach for tricuspid valve surgery, as authors suggest, should focus on the mechanisms of tricuspid regurgitation, which are unique to each given patient. For example, the surgical management of a cleft tricuspid valve (another well-known congenital entity) would be different from a case of tricuspid valve dysplasia when the mechanism of tricuspid regurgitation is a tethered anterior leaflet of tricuspid valve, which is failure of delamination issue.
We recognize this manuscript as an excellent resource for isolated tricuspid valve regurgitation; we would nonetheless underscore that congenital tricuspid valve disease (other than Ebstein anomaly) may be more common than anticipated, and may masquerade as primary idiopathic tricuspid regurgitation. We believe (likely as do the authors) that evaluation of all presumed isolated tricuspid valve disease deserves assessment by cardiologists expert in such distinction and classification.
1. Fender EA, Zack CJ, Nishimura RA. Isolated tricuspid regurgitation: outcomes and therapeutic interventions. Heart 2017.
2. Becker AE, Becker MJ, Edwards JE. Pathologic spectrum of dysplasia of the tricuspid valve. Features in common with Ebstein's malformation. Arch Pathol 1971;91:167-78.
3. Said SM, Burkhart HM, Dearani JA. Surgical management of congenital (non-Ebstein) tricuspid valve regurgitation. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2012;15:46-60.
4. Dearani JA, Danielson GK. Congenital Heart Surgery Nomenclature and Database Project: Ebstein's anomaly and tricuspid valve disease. Ann Thorac Surg 2000;69:S106-17.
We have read the interesting article from Bokma and colleagues [1] documenting the outcomes of pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot (rTOF). In this large multi-centre rTOF cohort, PVR was not associated with a reduced rate of death at mid-term follow-up. Additionally, authors highlighted that there were more events after PVR compared with no PVR in subjects not meeting consensus criteria.
Currently, although the overall hemodynamic benefits of PVR are evident with broad consensus for surgery before clinical deterioration or symptoms develop, uncertainties remain about the optimal timing for PVR.
Haemodynamic assessment surrounding PVR has focused on assessment of the right ventricle (RV) size and function, with the goal of intervening in patient prior to the development of irreversible RV deterioration failure. However, although the concept of using RV volumes for decision-making for PVR is widely used, its evidence regarding its impact on long-term outcomes remains weak.
New information about optimal PVR timing has been continuously addressed. A cardiac magnetic resonance based study suggested that a preoperative RVESVi cutoff of ≤82 mL/m2 was equally sensitive and more specific for normalization of RV volumes compared with our preoperative RVEDVi threshold of ≤158 mL/m2, justifying the use of RVESVi for clinical timing for PVR [2]. In 2015, Bokma concluded that preoperative RVESVi < 80 mL/m2 was the best thr...
We have read the interesting article from Bokma and colleagues [1] documenting the outcomes of pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot (rTOF). In this large multi-centre rTOF cohort, PVR was not associated with a reduced rate of death at mid-term follow-up. Additionally, authors highlighted that there were more events after PVR compared with no PVR in subjects not meeting consensus criteria.
Currently, although the overall hemodynamic benefits of PVR are evident with broad consensus for surgery before clinical deterioration or symptoms develop, uncertainties remain about the optimal timing for PVR.
Haemodynamic assessment surrounding PVR has focused on assessment of the right ventricle (RV) size and function, with the goal of intervening in patient prior to the development of irreversible RV deterioration failure. However, although the concept of using RV volumes for decision-making for PVR is widely used, its evidence regarding its impact on long-term outcomes remains weak.
New information about optimal PVR timing has been continuously addressed. A cardiac magnetic resonance based study suggested that a preoperative RVESVi cutoff of ≤82 mL/m2 was equally sensitive and more specific for normalization of RV volumes compared with our preoperative RVEDVi threshold of ≤158 mL/m2, justifying the use of RVESVi for clinical timing for PVR [2]. In 2015, Bokma concluded that preoperative RVESVi < 80 mL/m2 was the best threshold to achieve mid-to-late RV normalization [3]. The impact of abnormal RV mechanics on the LV has been appreciated, with the assessment of LV assuming higher priority in decision-making.
Interestingly, another study from INDICATOR cohort [4] found previous implantation of RV-pulmonary artery conduits was associated with adverse outcomes rather than RV volumes. Age at TOF repair was also identified as risk factor for post-PVR arrhythmia. It’s well summarized that TOF anatomical variants, trans-ventricular repair and preoperative cyanosis were also know as determinants for PVR outcomes [2].
Hence more information could be further illustrated, including the baseline anatomical and surgical features of TOF repair, the surgical techniques of PVR and their potential relationship with PVR outcomes. Moreover, additional comments about this issue would be helpful.
[1] Bokma JP, Geva T, Sleeper LA, et al. Heart Published Online First: [1-Nov-2017]. doi:10.1136/ heartjnl-2017-312048.
[2] Heng EL, Gatzoulis MA, Uebing A, et al. Immediate and Midterm Cardiac Remodeling After Surgical Pulmonary Valve Replacement in Adults With Repaired Tetralogy of Fallot: A Prospective Cardiovascular Magnetic Resonance and Clinical Study. Circulation. 2017;136:1703-1713.
[3] Bokma JP, Winter MM, Oosterhof T, et al. Pre-operative thresholds for mid-to-late haemodynamic and clinical outcomes after pulmonary valve replacement in tetralogy of Fallot. Eur Heart J. 2016;37(10):829-35.
[4] Valente AM, Gauvreau K, Assenza GE, et al. Contemporary predictors of death and sustained ventricular tachycardia in patients with repaired tetralogy of Fallot enrolled in the INDICATOR cohort. Heart 2014;100:247–253.
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
Martínez –Milla el al, report an interesting case of cardiac lymphoma, presenting as complete AV block.
A close look at the electrocardiogram, reveals a P wave with a normal frontal axis, broad (duration > 120 ms), and bimodal ( notched). These are the diagnostic hallmarks of partial interatrial block (IAB).
In this patient, the lymphoma probably infiltrates the Bachmann’s bundle, interrupting the preferential pathway of left atrial activation, causing partial IAB.
Although often overlooked, IAB is frequent in the elderly, and it is associated with atrial arrhythmias and stroke.
Because the diagnosis of IAB relies on the morphology and duration of the P wave, a meticulous analysis of the electrocardiogram is mandatory.
The recommendation that combined antiplatelet and new oral anticoagulant(NOAC) therapy should rely on the lowest approved NOAC dose effective for stroke prevention(1) is one which favours low-dose edoxaban instead of either dabigatran, rivaroxaban, or apixaban, when reduction of risk of gastrointestinal(GIT) bleeding is taken into account. In a review of clinical experience of bleeding associated with NOACs(dabigatran, rivaroxaban, apixaban, and edoxaban) versus warfarin in nonvalvular atrial fibrillation(NVAF), edoxaban 30 mg/day was the only antithrombotic agent associated with significantly(p < 0.001) lower risk of GIT bleeding than warfarin(Hazard Ratio: 0.67;95% Confidence Interval 0.53 to 0.83). For apixaban and for dabigatran 110 mg BID, the risk of GIT bleeding was comparable with the risk associated with warfarin use. For rivaroxaban and for dabigatran 150 mg BID the risk of GIT haemorrhage was significantly higher(P < 0.0001, and p < 0.001, respectively) than the GIT bleeding risk associated with warfarin(2).
Show MoreIn a study where 92.2% of 5301 NVAF users of antiplatelet agents were prescribed a NOAC in combination with only one antiplatelet agent vs 86.3% of 9106 NVAF users of antiplatelet agents who were prescribed warfarin with only one antiplatelet agent , concomitant antiplatelet and NOAC use was associated with significantly lower risk of intracranial bleeding than concomitant antiplatelet and warfarin use(HR 0.68, 95% CI, 0.51 to 0.91). Ne...
We read with interest the article by Rusingiza et al (1)and report our experience from Northern Sri Lanka, a Low Middle Income Country (LMIC). Sri Lanka had invested heavily in free education and healthcare with demonstrably high literacy rates and positive health indices (2). However, the focus of the healthcare related investment has been in the secondary and tertiary care institutions, whilst primary care systems remain poorly developed. Northern Sri Lanka had been further impacted adversely by three decades of civil strife.
Show MoreWe report our experience in the management of post-valvular surgery patients at the Jaffna Teaching Hospital, the only tertiary referral centre for the region. Improvements in socioeconomic conditions has resulted in a decline in the incidence of rheumatic heart disease in Sri Lanka which accounted for only 0.34% of all deaths in 2017 (3). Concurrently, established patients receiving prosthetic heart valves has increased mainly due to improving access to surgical facilities. Unfortunately, Northern Sri Lanka had been without facilities for cardiac surgery for three decades leaving patients to access facilities elsewhere in the country. Post-surgery follow-up occurred primarily in Jaffna and a few other secondary care hospitals in the region. Unlike in the Rwandan study, most of our patients received parenteral penicillin prophylaxis thereby enhancing compliance and were fitted with metallic rather than bioprosthetic valves, thereby necessitat...
There was significantly higher usage of both loop diuretics and aldosterone antagonist in the group with persistent hyponatraemia. Is it possible that one of the clinical manifestation of RV dysfunction, i.e peripheral oedema, led to an increased use of diuretic in this group and hence hyponatraemia as a complication of this treatment? Over diuresis in this scenario leads to activation of the RAAS which in turn worsens pulmonary hypertension and tricuspid regurgitation. The consequence of this is worsening peripheral oedema and the tendency to increase the diuretic dose.Hyponatraemia therefore may not be an independent predictor of outcome as stated.
We read with great interest the article by Elias et al (1) regarding the longer term clinical outcomes from the EXPLORE trial. The authors are to be congratulated for conducting this important study to address the optimal management of patients presenting with a concurrent CTO in a non-infarct related artery (non-IRA) during a STEMI. The results at 1 year are similar to those in the initial 4 month outcome (2), with no difference in the primary endpoints of cardiac MRI determined LVEF or LVEDV in either CTO-PCI and CTO-No PCI groups. At a median of 3.9 years, there was no difference in long term MACE, although an apparent increase in cardiovascular mortality (6% vs 1%, p=0.02).
Whilst this important study adds to the much needed literature on randomised studies related to PCI of CTOs, the results should be interpreted with caution. Firstly, large scale contemporaneous studies in CTO PCI have had procedural success rates in the region of 90% (3), whilst in EXPLORE (2) this rate was considerably lower, at 73% by core laboratory. This suggests either a more anatomically complex subset of patients, or else attempts by non-dedicated CTO PCI operators, both of which affect the interpretation of the intention to treat population.
Furthermore, the mortality data should be reviewed with care. At 12 months, there were 4 cardiovascular deaths (2.7%) in the CTO PCI group, with no deaths in the CTO-No PCI groups. These rates are significantly lower compared with other t...
Show MoreI read with great interest the paper by Elias et al regarding the mid-term and long-term clinical outcome of the Evaluating Xience and left ventricular function in Percutaneous Coronary Interventions on occlusiOns afteR ST elevation myocardial infarction (EXPLORE) trial. [1] The authors are to be congratulated for this detailed analysis evaluating the effect of chronic total occlusions – percutaneous coronary intervention (CTO-PCI) compared with CTO-No PCI on clinical outcome, left ventricular function and angina status in patients with ST elevation myocardial infarction (STEMI) with a concurrent CTO. The message of their study is that early CTO-PCI in patients with STEMI presenting with a concurrent CTO during primary PCI should not be performed routinely.
Show MoreThe authors also analysed the study population combined and found higher long-term mortality in patients who were older (>60 years) (11% vs 3%; HR 3.74; 95% CI 1.37 to 10.21; P=0.01), who had diabetes (15% vs 6%; HR 2.94; 95% CI 1.19 to 7.30; P=0.02), had a higher left ventricular enddiastolic volume at baseline (12% vs 1%; HR 13.04; 95% CI 1.70 to 100.30; P=0.01) and who had a high SYNTAX score (10% vs 4%; HR 2.50; 95% CI 1.01 to 6.20; P=0.048). They also stated that cardiac death was more frequent in the CTO-PCI arm (6.0% vs 1.0%, P=0.02) with no difference in all-cause mortality. However, it is known that a major prognostic factor in STEMI patients with a concurrent CTO is the presence of collateral feeding...
We thank dr. Katsouras for his response to our long-term EXPLORE manuscript (1). We agree that in the ST-segment elevation (STEMI) population the presence of collaterals to the concurrent chronic total occlusion (CTO) is of prognostic relevance. We previously reported in 413 consecutive STEMI patients with a CTO that the presence of well-developed collaterals to the CTO compared to poorly developed collaterals was associated with improved outcome. We also assessed the influence of the collateral origin on survival, as collaterals coming distally from the culprit lesion are (partially) blocked during the acute phase of STEMI. In 16% of the patients the collaterals originated directly or distal from the culprit lesion and these patients had a lower survival compared to the patients in whom the collaterals were not blocked during STEMI (2).
In the EXPLORE trial patients with well-developed collaterals to the CTO had a significantly better left ventricular (LV) function at 4 months follow-up. Nonetheless, we did not find a significant treatment effect of CTO-PCI on global LV function nor on clinical outcome in patients with poorly developed nor with well-developed collaterals (3). On a regional level we found that the recovery of segmental wall thickening of the dysfunctional CTO myocardium was better in patients with well-developed collaterals. However, no significant interaction of collateral quality on the effect of CTO PCI was found (4). In EXPLORE there were 34 p...
Show MoreWe read with interest the excellent and timely article on increasingly detected cases of isolated tricuspid valve regurgitation (1) . The authors rightly note that there is an emerging population of adult patients without left-sided heart disease, pulmonary hypertension or congenital abnormalities who develop symptomatic isolated tricuspid regurgitation. While this is true, we believe that a proportion of these cases of isolated tricuspid regurgitation may well be congenital in origin.
Show MoreThe spectrum of congenital abnormalities of tricuspid valve abnormalities is large (2), and while Ebstein anomaly and tricuspid valve anomalies associated with atrioventricular septal defects and pulmonary atresia are the most commonly discussed, there is a group of patients with tricuspid valve dysplasia or congenitally abnormal tricuspid valves that are under-recognized. Said et al (3) and Dearani et al (4) from the authors’ institution have previously discussed the wide spectrum of congenital tricuspid valve anomalies. The importance of recognizing this group of cases as a separate entity is twofold. One that tricuspid valve dysplasia from failure of delamination of the tricuspid valve, like Ebstein anomaly can be associated with cardiomyopathy and arrhythmia and other congenital anomalies can be missed if focus if just on the valve. Secondly, surgical approach for tricuspid valve surgery, as authors suggest, should focus on the mechanisms of tricuspid regurgitation, which are uni...
We have read the interesting article from Bokma and colleagues [1] documenting the outcomes of pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot (rTOF). In this large multi-centre rTOF cohort, PVR was not associated with a reduced rate of death at mid-term follow-up. Additionally, authors highlighted that there were more events after PVR compared with no PVR in subjects not meeting consensus criteria.
Show MoreCurrently, although the overall hemodynamic benefits of PVR are evident with broad consensus for surgery before clinical deterioration or symptoms develop, uncertainties remain about the optimal timing for PVR.
Haemodynamic assessment surrounding PVR has focused on assessment of the right ventricle (RV) size and function, with the goal of intervening in patient prior to the development of irreversible RV deterioration failure. However, although the concept of using RV volumes for decision-making for PVR is widely used, its evidence regarding its impact on long-term outcomes remains weak.
New information about optimal PVR timing has been continuously addressed. A cardiac magnetic resonance based study suggested that a preoperative RVESVi cutoff of ≤82 mL/m2 was equally sensitive and more specific for normalization of RV volumes compared with our preoperative RVEDVi threshold of ≤158 mL/m2, justifying the use of RVESVi for clinical timing for PVR [2]. In 2015, Bokma concluded that preoperative RVESVi < 80 mL/m2 was the best thr...
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...
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