we read with deep interest the paper by Marcadé-Besora[1] and collaborators, providing extremely reliable evidence in favour of a long-term protective effect of SARS-CoV-2 vaccination, against cardiovascular events (especially thrombosis-related ones), in patients recovering from an acute SARS-CoV-2 infection.
Such protective affect remains significant up to one year after acute infection, and this not only indirectly confirms that the well-recognized thrombophylic disturbance associated to SARS-CoV-2 lasts actually longer than initially thought[2], but also suggests that this is - at least in part - preventable, through immune mechanisms.
In the study, the follow-up ended on the first post-COVID outcome event, so occasional SARS-CoV-2 reinfections, occurring more often in the unvaccinated individuals, cannot be the reason for the observed differences between groups.
The authors did not stratify results according to the number of vaccine doses received: we suggest this analysis to be done. In fact, viral neutralization efficacy conferred by COVID vaccines is not “all-nothing” and depends on time since last booster and on number of doses received[3]: should the cardiovascular protective effect observed by the authors follow the same pattern, this would add a strong evidence in favour of its linkage to vaccination, instead of other potentially associated confounders.
In a different setting, and a much smaller scale, we also obs...
we read with deep interest the paper by Marcadé-Besora[1] and collaborators, providing extremely reliable evidence in favour of a long-term protective effect of SARS-CoV-2 vaccination, against cardiovascular events (especially thrombosis-related ones), in patients recovering from an acute SARS-CoV-2 infection.
Such protective affect remains significant up to one year after acute infection, and this not only indirectly confirms that the well-recognized thrombophylic disturbance associated to SARS-CoV-2 lasts actually longer than initially thought[2], but also suggests that this is - at least in part - preventable, through immune mechanisms.
In the study, the follow-up ended on the first post-COVID outcome event, so occasional SARS-CoV-2 reinfections, occurring more often in the unvaccinated individuals, cannot be the reason for the observed differences between groups.
The authors did not stratify results according to the number of vaccine doses received: we suggest this analysis to be done. In fact, viral neutralization efficacy conferred by COVID vaccines is not “all-nothing” and depends on time since last booster and on number of doses received[3]: should the cardiovascular protective effect observed by the authors follow the same pattern, this would add a strong evidence in favour of its linkage to vaccination, instead of other potentially associated confounders.
In a different setting, and a much smaller scale, we also observed a possible benefit of SARS-CoV-2 vaccination towards late post-COVID thrombotic events. In our study[4], we followed-up a cohort of 1515 patients, recovering from COVID-19, for 18 months into recovery. All of them acquired SARS-CoV-2 infection in the very first wave, long before any vaccine was available, but almost all of them were finally vaccinated (n = 1349; 89%), at a median of 9.6 months after natural infection (IQR: 8.3 - 10.8).
We defined a composite outcome ("outcome events", OEs), including: cerebral o cardiac ischemia, venous or arterial thrombosis of any site, pulmonary embolism, cardiac arrhythmia, heart failure (almost the same events considered in the paper by Marcadé-Besora), and we tracked the occurrence of OEs from the end of the "early post-acute" phase, until 18 months after infection.
Among 1515 patients, we identified 84 OEs occurring to 75 patients (5%). Patients meeting any OE were more often unvaccinated (28.9% of the 166 unvaccinated, versus 2.0% of the 1349 vaccinated, p < 0.001), and the number of doses received was inversely associated to OEs (no doses versus 1, 2 or 3 doses – p for trend < 0.001). This association remained stable, even after matching each vaccinated patient to one unvaccinated control, by age, gender and previous history of any OE (data not published). A multivariable Cox proportional hazard model (including vaccine as a time-dependent variable) did not prove the effect of vaccines to be independently associated with a reduced risk of OEs (HR=0.81, 95% CI 0.24-2.66, p=0.72), probably because of the retrospective nature of the study and the multiple possible confounding factors, still in the light of the findings by Marcadé-Besora and collaborators, our findings may suggest that the type of immunity enhanced by vaccination may have been beneficial in counteracting post-COVID immuno-thrombosis, also when received many months after natural infection, in the first pandemic waves.
It is temptative to speculate that the persisting efficacy of the “original variant” vaccines against the most severe forms of COVID-19, in spite of a waning neutralizing efficacy against the new variants[5], may have something to do with this indirect effect of anti-SARS-CoV-2 vaccination.
REFERENCES
1. Mercadé-Besora N, Li X, Kolde R, et alThe role of COVID-19 vaccines in preventing post-COVID-19 thromboembolic and cardiovascular complicationsHeart 2024;110:635-643.
2. Fan BE, Wong SW, Sum CLL, et al. Hypercoagulability, endotheliopathy, and inflammation approximating 1 year after recovery: Assessing the long-term outcomes in COVID-19 patients. Am J Hematol. 2022 Jul;97(7):915-923. doi: 10.1002/ajh.26575.
3. Rahman MO, Kamigaki T, Thandar MM et al. Protection of the third-dose and fourth-dose mRNA vaccines against SARS-CoV-2 Omicron subvariant: a systematic review and meta-analysis. BMJ Open. 2023 Dec 20;13(12):e076892. doi: 10.1136/bmjopen-2023-076892.
4. Benatti SV, Venturelli S, Crotti G, et al. Clinical variables associated with late-onset thrombotic and cardiovascular events, after SARS-CoV-2 infection, in a cohort of patients from the first epidemic wave: an 18-month analysis on the "Surviving-COVID" cohort from Bergamo, Italy. Front Cardiovasc Med. 2023 Nov 30;10:1280584. doi: 10.3389/fcvm.2023.1280584.
5. DeCuir J, Surie D, Zhu Y, et al. Effectiveness of Monovalent mRNA COVID-19 Vaccination in Preventing COVID-19-Associated Invasive Mechanical Ventilation and Death Among Immunocompetent Adults During the Omicron Variant Period - IVY Network, 19 U.S. States, February 1, 2022-January 31, 2023. MMWR Morb Mortal Wkly Rep. 2023 Apr 28;72(17):463-468. doi: 10.15585/mmwr.mm7217a3. PMID: 37104244.
A trial of loop diuretic therapy in patients who have not received the benefit of evaluation either by echocardiography or by natriuretic peptide testing can be an opportunity to maximise alternative strategies for validating the diagnosis of congestive heart failure(CHF)
The following are some of the alternative strategies:-
(1)Evaluation of jugular venous pressure(JVP).
This strategy was poorly maximised in the anecdotal report of two patients(patient 2 and patient 3) ,with peripheral oedema and breathlessness, in whom the initial cardiovascular examination was recorded as "normal". A subsequent repeat clinical examination revealed an extremely elevated JVP attributable to constrictive pericarditis[1].
Documentation of body weight before and after a trial of loop diuretic treatment enhances the diagnostic value of evaluation of JVP. The rationale is that a JVP that is persistently high in spite of significant weight loss after diuretic use can be a powerful indicator of the diagnosis of constrictive pericarditis[2]]
(ii) Documentation of a fall in forced vital capacity(FVC) after a trial of loop diuretic treatment.
In that context, a fall in body weight which is accompanied by a fall in FVC after a trial of loop diuretic treatment is indicative of a reversible restrictive ventilatory defect that is attributable to pulmonary congestion and, hence, CHF. Reversibility of FVC after loop diuretics is a well document...
A trial of loop diuretic therapy in patients who have not received the benefit of evaluation either by echocardiography or by natriuretic peptide testing can be an opportunity to maximise alternative strategies for validating the diagnosis of congestive heart failure(CHF)
The following are some of the alternative strategies:-
(1)Evaluation of jugular venous pressure(JVP).
This strategy was poorly maximised in the anecdotal report of two patients(patient 2 and patient 3) ,with peripheral oedema and breathlessness, in whom the initial cardiovascular examination was recorded as "normal". A subsequent repeat clinical examination revealed an extremely elevated JVP attributable to constrictive pericarditis[1].
Documentation of body weight before and after a trial of loop diuretic treatment enhances the diagnostic value of evaluation of JVP. The rationale is that a JVP that is persistently high in spite of significant weight loss after diuretic use can be a powerful indicator of the diagnosis of constrictive pericarditis[2]]
(ii) Documentation of a fall in forced vital capacity(FVC) after a trial of loop diuretic treatment.
In that context, a fall in body weight which is accompanied by a fall in FVC after a trial of loop diuretic treatment is indicative of a reversible restrictive ventilatory defect that is attributable to pulmonary congestion and, hence, CHF. Reversibility of FVC after loop diuretics is a well documented feature of CHF[3],[4].
(iii)Lung ultrasound for detection of "B" lines before and after loop diuretics[5],[6]. In one meta analysis a comparison of point of care lung ultrasound versus chest X-ray generated the following results for detection of cardiogenic pulmonary oedema:-
Pooled Sensitivity of Cardiac ultrasound 91.8%(95% Confidence Interval 80.5% to 96.8%) versus pooled sensitivity of Chest X-ray amounting to 76.5%(95% CI 67.2% to 83.7%)[6].
Pooled specificity of lung ultrasound amounted to 92.3%(95% CI 86.6% to 95.7%) versus chest X-ray specificity amounting to 87%(95% CI 79.3% to 92.1%).[[6].
However, notwithstanding the retrospective observation that, in the short term, the outcome of patients treated with loop diuretics was the same regardless of whether or not they had a recorded diagnosis of heart failure[7], validation of CHF diagnosis by the above strategies{1-6} should always culminate in a documentation of left ventricular ejection fraction. The rationale is that published evidence indicates that there is a significant survival benefit when CHF treatment is tailored to left ventricular ejection fraction status.
I have no conflict of interest
References
[1]Lowe MD., Harcombe AA., Grace AA., Petch MC
Restrictive constrictive heart failure masquerading as liver disease
BMJ 1999;3018:585-586
[2]Conti CR., Friesinger GC
Chronic constrictive pericarditis clinical and laboratory findings in 11 cases
Johns Hopkins Med J 1967;120;262-274
[3]Light RW. George RB
Serial pulmonary function in patients with acute heart failure
Arch Intern Med 1983;143:429-433
[4]Adaghir RA., Abdelkadir WA., Kassem SE., Marbut MM
The effect of diuretics on spitometric parameters in patiets with ischemic heart disease
Tikrit Journal of Pharmaceutical Sciences 2012;8:15-21
[5]Volpicelli G., Caramello V., Cardinale L et al
Bedside ultrasound of the lung for the monitoring of acute decompensated heart failure
Am J Emerg Med 2008;26:585-591
[6[]Chiu L., Jairam MP., Chow R et al
Meta-analysis of point of care lung ultrasoonography versus chest radiography in adults with symptoms of acute decompensated heat failure
Am J Cardiol 2022;174:89-95
[7]Cuthbert JJ., Soyiri I.Lomax J et al
Outcomes in patients treated with loop diuretics without a diagnosis of heart failure: a retrospective cohort study
The assertion that natriuretic peptide levels below a defined threshold(for, example, Brain Natriuretic Peptide(BNP) levels < 100 pg/mL) can safely rule out heart failure and may also obviate the need to proceed to early echocardiography[1] should be qualified as follows:-
Early echocardiography does not necessarily confirm or refute the diagnosis of congestive heart failure(CHF) in patients with heart failure characterised by preserved ejection fraction(HFpEF). This is a truism that ought to be valid even in HFpEF patients with BNP levels < 100 pg/mL[2]. In the latter study , among 159 patients who had been hospitalised for CHF, the latter characterised by left ventricular ejection fraction(LVEF) amounting to >50%, in association with pulmonary capillary wedge pressure > 15 mm Hg, 46/159 patients(29%) had BNP equal to or less than 100 pg/mL[2].. Accordingly, if the index of suspicion for CHF is sufficiently high strategies other than echocardiography should be deployed to confirm or refute the diagnosis of CHF. The following are some of those strategies:-
(i) Clinical evaluation of jugular venous pressure(JVP). A raised JVP is indicative of a right atrial pressure beyond the normal upper limit of 8 mm Hg[3]. Furthermore, jugular venous distension is associated with a likelihood ratio amounting to 5.1(95% Confidence Interval, 3.2 to 7.9) in favour of a diagnosis of CHF[4].
(ii)Evaluation of inferior vena cava(IVC) diameter. An...
The assertion that natriuretic peptide levels below a defined threshold(for, example, Brain Natriuretic Peptide(BNP) levels < 100 pg/mL) can safely rule out heart failure and may also obviate the need to proceed to early echocardiography[1] should be qualified as follows:-
Early echocardiography does not necessarily confirm or refute the diagnosis of congestive heart failure(CHF) in patients with heart failure characterised by preserved ejection fraction(HFpEF). This is a truism that ought to be valid even in HFpEF patients with BNP levels < 100 pg/mL[2]. In the latter study , among 159 patients who had been hospitalised for CHF, the latter characterised by left ventricular ejection fraction(LVEF) amounting to >50%, in association with pulmonary capillary wedge pressure > 15 mm Hg, 46/159 patients(29%) had BNP equal to or less than 100 pg/mL[2].. Accordingly, if the index of suspicion for CHF is sufficiently high strategies other than echocardiography should be deployed to confirm or refute the diagnosis of CHF. The following are some of those strategies:-
(i) Clinical evaluation of jugular venous pressure(JVP). A raised JVP is indicative of a right atrial pressure beyond the normal upper limit of 8 mm Hg[3]. Furthermore, jugular venous distension is associated with a likelihood ratio amounting to 5.1(95% Confidence Interval, 3.2 to 7.9) in favour of a diagnosis of CHF[4].
(ii)Evaluation of inferior vena cava(IVC) diameter. An IVC diameter amounting to 20 mm is associated with 73% sensitivity and 85% specificity for predicting a right atrial pressure of > 10 mm Hg[5] In another study, among 110 patients fulfilling the European Society of Cardiology criteria for acute heart failure, comparable values for IVC diameter(mean values of 20-21 mm) were found among 59 patients with LVEF equal to or less than 40% versus 51 counterparts with LVEF > 40% even though the latter subgroup had significantly(p < 0.0001) lower BNP levels(mean levels 1132 pg/mL vs 415 pg/mL)[6]..
Evaluation of patients with normal BNP despite clinical suspicion of CHF should also include a diligent search for stigmata of constrictive pericarditis(CP). The latter is a disorder characterised by marked elevation of JVP which persists despite a response to diuretic treatment that is characterised by pronounced weight loss[7].. Accordingly, the association of persistently high JVP and normal or only modestly elevated lvels of BNP should always raise the index of suspicion for CP. In Melo et al, where 91% of 24 CP subjects had high JVP levels, mean BNP(obtained in 22 subjects) amounted to 170 pg/mL(range 37-468 pg/mL). In the light of those observations the authors commented that "the presence of right heart failure with preserved ejection fraction and BNP levels normal or slightly elevated may suggest the diagnosis[of CP], even with a normal TE(transthoracic echocardiogram)"[8].
I have no funding and no conflict of interest
References
[1]Eltayeb M., Squire I., Sze S
Biomarkers in heart failure: a focus on natriuretic peptides
Heart
6th September 2023
doi:10.1136/heartjnl-2020-318553
[2]Anjan VY., Loftus TM., Burke MA et al
Prevalence, clinical phenotype, and outcomes associated with normal B type natriuretic peptide levels in heart failure with preserved ejection fraction
Am J Cardiol 2012;110:870-875
[3]Sinisalo J., Rapola J., Rossinen J., Kupari M
Simplifying the estimation of jugular venous pressure
Am J Cardiol 2007;100:1779-1781
[4]Wang CS., Fitzgerald JM., Schulzer M., Mak E., Ayas NT
Does this dyspneic patient in the emergency department have congestive heart failure?
JAMA 2005;294:1944-1956
[5] Brennan J., Blair JE., Goonewardena S et al
Reappraisal of the use of inferior vena cava for estimating right atrial pressure
J Am Soc Echocardiography 2007;20:857-861
[6]Coiro S., Porot G., Rossignol P et al
Prognostic value of pulmonary congestion assessed by lung ultrasound imaging during heart failure hospitalisation: A two centre cohort study
SCIENTIFIC REPORTS
DOI:10.1038/srep39426
[7] Jolobe OMP
Monitoring of the jugular venous pressure response to diuretics in constrictive pericarditis
Int J Cardiol 2015;182:163
[8] Melo DTP., Fernandes F., Salemi VMC et al
Diagnostic challenge in constrictive pericarditis: the role of brain natriuretic peptide and image tools
Eur Heart J 2013;34;Suppl_1:P3893
dio.org/10.1093/eurheartj/eht309.P3893
Notwithstanding the assertion that the N-terminal pro-BNP-type natriuretic peptide(NT-proBNP) is highly sensitive and has excellent negative predictive value for heart failure(HF)[1], the following caveats may apply:-
Firstly, the negative predictive value of NT-pro BNP is severely curtailed in HF patients who are obese(BMI 30.0 or more), with the consequence that low blood levels of that biomarker do not rule out a diagnosis of HF with preserved ejection fraction(HFpEF)[2]. In the latter study there were 30 patients with left ventricular ejection fraction of 50% or more who had complied with the European Society of Cardiology diagnostic criteria for HF. Twenty nine of the patients had a Body Mass Index(BMI) of 30.0 or more, and one had a BMI of 27(ie oeversight but not obese). Fifteen of the patients had NT-proBNP levels amounting to < 125 pg/ml[2]
In the absence of the confounding effect of obesity, levels of NT-pro BNP below the diagnostic cut off level of 400 pg/ml also appear to be more prevalent in HFpEF patients than in patients with heart failure with reduced ejection fraction(HFrEF) [3]. In the latter study a comparison was made between 65 HFpEF patients and 50 patients with HFrEF. Mean values for BMI amounted to 24 in both subgroups. Criteria for HFpEF comprised symptoms of HF in association with echocardiographic documentation of an E/A ratio < 1 and left ventricular ejection fraction(LVEF) of 50% or more.. Criteria for HFr...
Notwithstanding the assertion that the N-terminal pro-BNP-type natriuretic peptide(NT-proBNP) is highly sensitive and has excellent negative predictive value for heart failure(HF)[1], the following caveats may apply:-
Firstly, the negative predictive value of NT-pro BNP is severely curtailed in HF patients who are obese(BMI 30.0 or more), with the consequence that low blood levels of that biomarker do not rule out a diagnosis of HF with preserved ejection fraction(HFpEF)[2]. In the latter study there were 30 patients with left ventricular ejection fraction of 50% or more who had complied with the European Society of Cardiology diagnostic criteria for HF. Twenty nine of the patients had a Body Mass Index(BMI) of 30.0 or more, and one had a BMI of 27(ie oeversight but not obese). Fifteen of the patients had NT-proBNP levels amounting to < 125 pg/ml[2]
In the absence of the confounding effect of obesity, levels of NT-pro BNP below the diagnostic cut off level of 400 pg/ml also appear to be more prevalent in HFpEF patients than in patients with heart failure with reduced ejection fraction(HFrEF) [3]. In the latter study a comparison was made between 65 HFpEF patients and 50 patients with HFrEF. Mean values for BMI amounted to 24 in both subgroups. Criteria for HFpEF comprised symptoms of HF in association with echocardiographic documentation of an E/A ratio < 1 and left ventricular ejection fraction(LVEF) of 50% or more.. Criteria for HFrEF comprised symptoms of heart failure in association with LVEF < 50%. In the HFpEF subgroup the mean value of NT proBNP amounted to 213.32 pg/ml(range 12.35-633.57) versus 308.45 pg/ml(range 205.75-1068.61 pg/ml) in the HFrEF subgroup. The difference was statistically different(p < 0.001)[3].
Conversely, blood levels of NT-proBNP may be elevated in patients who have acute exacerbations of chronic obstructive pulmonary disease(COPD) even in the absence of concomitant left ventricular dysfunction[4]. In the latter study there were 104 patients with the association of acute exacerbation of COPD and high NT-proBNP levels(mean value 1707 pg/ml). All 104 subjects had left ventricular ejection fraction >50%. Furthermore, 36 subjects(35%) had no evidence of left ventricular diastolic dysfunction[4].
Pulmonary embolism is another well documented cause of an increase in the blood levels of NT-proBNP[5]. In the latter study NT-proBNP levels of 600 pg/ml or more were documented in 353 subjects with pulmonary embolism, only 53 of whom had concomitant HF[5].
I have no funding and no conflict of interest
References
[1]Doherty DJ., Docherty KF., Gardner RS
Review of th National Institute for Health and Care Excellence guidelines on chronic heart failure
Heart 2024;110;466-475
[2]Buckley LF., Canada JM., Del Buono MG et al
Low NT-proBNP lebels in overweight and obese patients do not rule out a diagnosis of heart failure with preserved ejection fraction
ESC Heart Failure 2018;5:372-378
[3]Cui K., Huang W., Fan J., Lei H
Midregional pro-atrial natriuretic peptide is a superior biomarker to N-terminal pro-B-type natriuretic peptide in the diagnosis of heart failure patients with preserved ejection fraction
Medicine 2018;97:36(e12277).
[4]Adrish M., Nannaka VB., Cano E et al
Significance of NT-pro-BNP in acute exacerbation of COPD patients without underlying left ventricular dysfunction
International Journal of Chronic Obstructive Pulmonary Disease 2017;12:1183-1189
[5]Lankeit M., Jimenez D., Kostrubiec M et al
Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism
Eur Respir J 2014;43:1669-1677
Notwithstanding the fact that Blagova et al did not identify any specific findings related to eosinophilic myocarditis(EM) in their series of 14 patients with post-COVID myoendocarditis[1], anecdotal reports not cited by Techasatian et al[2] have documented an association between COVID 19 infection and eosinophilic myocarditis[3-5].
Craver et al reported the case of a previously healthy 17 year old male who had a 2 day history of headache, nausea and vomiting , followed by sudden death. At autopsy his heart weighed 500 grams(expected weight fro age was 262-295 grams), with a histological profile characterised by an inflammatory infiltrate which had prominent" eosinophils, in addition to lymphocytes and macrophages. This was associated with multiple foci of myocyte necrosis.. Histological examination of the lungs revealed mild chronic inflammation of the bronchi with only occasional eosinophils. Postmortem nasopharyngeal swabs tested positive for SARS-2 CoV-2[3].
In two other cases of the association of COVID-19 infection and eosinophilic myocarditis, each of the patients[4],[5] had a previous history of chronic asthma, thereby raising the possibility that eosinophilic myocarditis might have been a manifestation of eosinophilic granulomatosis with polyangiitis.
However, given the fact that, in its own right, COVID-19 infection can be a trigger for eosinophilic pneumonia[6], the association of eosinophilic myocarditis and COVID-19 infectio...
Notwithstanding the fact that Blagova et al did not identify any specific findings related to eosinophilic myocarditis(EM) in their series of 14 patients with post-COVID myoendocarditis[1], anecdotal reports not cited by Techasatian et al[2] have documented an association between COVID 19 infection and eosinophilic myocarditis[3-5].
Craver et al reported the case of a previously healthy 17 year old male who had a 2 day history of headache, nausea and vomiting , followed by sudden death. At autopsy his heart weighed 500 grams(expected weight fro age was 262-295 grams), with a histological profile characterised by an inflammatory infiltrate which had prominent" eosinophils, in addition to lymphocytes and macrophages. This was associated with multiple foci of myocyte necrosis.. Histological examination of the lungs revealed mild chronic inflammation of the bronchi with only occasional eosinophils. Postmortem nasopharyngeal swabs tested positive for SARS-2 CoV-2[3].
In two other cases of the association of COVID-19 infection and eosinophilic myocarditis, each of the patients[4],[5] had a previous history of chronic asthma, thereby raising the possibility that eosinophilic myocarditis might have been a manifestation of eosinophilic granulomatosis with polyangiitis.
However, given the fact that, in its own right, COVID-19 infection can be a trigger for eosinophilic pneumonia[6], the association of eosinophilic myocarditis and COVID-19 infection might be mediated by a hypersensitivity reaction to the SARS-2 CoV-2 virus. That would account for the development of eosinophilic myocarditis in the previously healthy 17 year old male in reported by Craver et al[3]. The same aetiopathogenic mechanism might, arguably, even have facilitated the development of eosinophilc myocarditis in the two patients with previous history of asthma[4],[5].
I have no funding and no conflict of interest.
References
[1]Blagova O., Lutokhina Y., Kogan E et al
Chronic biopsy-proven post-COVID myoendocarditis with SARS-CoV-2 persistence and high level of antiheart antibodies
Clin Cardiol 2022;45:952-959
[2]Techasatian W., Gozun M., Vo K et al
Eosinophilic myocarditis: systematic review
Heart 2023 doi:10.1136/heartjnl-2023-323225
[3]Craver R., Huber S., Sandomirsky M et al
Fatal eosinophilic myocarditis in a healthy 17-year old male with acute respiratory syndrome coronavirus 2 (SARS-CoV-2c)
FETAL AND PEDIATRIC PATHOLOGY doi.org/10.1080/15513815.20201761491
[4]Sherafan A., Rachmanian M., Badkoubeh RS et al
Hypereosinophilic syndrome and COVID-19:2 case reports
Journal of Cardiothoracic Surgery 2023:18;158
doi.org/10.1186/s13019-023-02241-1
[5]Rao K., Arustamyan M., Walling A et al
Utility of cardiac magnetic resonance imaging in diagnosing eosinophilic myocarditis in a patient recently recovered from COVID-19: a grand round case report
Eur Heart J Case Reports 2023;7:1-8
[6]Araujo M., Correia S., Lima AL et al
SARS-CoV-2 as a trigger of eosinophilic pneumonia
Pulmonology 2022;28:62-64
In view of the fact that the association of pulmonary embolism (PE) and chronic obstructive pulmonary disease (COPD) is one fraught with the risk of PE recurrence, and fatal outcome, respectively [1], the association of the two disorders is one that should have merited some mention in the review of heightened long term cardiovascular risk after exacerbations of COPD [2], notwithstanding the uncertainty about the true prevalence of PE in patients with COPD [3],[4] . The uncertainty about PE prevalence in COPD is, arguably, in part, attributable to the fact that some COPD patients have coexisting carcinomatosis as a risk factor for PE in its own right [3]. In a systematic review and meta-analysis published in 2009, Rizkallah et al documented a PE prevalence amounting to 19.9%(95% Confidence Interval 6.7% to 33%) among patients with acute exacerbations of COPD[4]. Anecdotal reports also document the association of right heart thrombi (one of the stigmata of pulmonary thromboembolism) and COPD [5-8].
Over and above its association with PE, COPD also appears to be a risk factor for the occurrence of "in situ" thrombosis in the pulmonary arterial vasculature [9],[10], a development which is a long term risk factor for right heart failure.
Arguably, in view of the prothrombotic environment generated by acute exacerbations of COPD, and the fact that atrial fibrillation might be prevalent in approximately 15% of COPD patients [2], there might b...
In view of the fact that the association of pulmonary embolism (PE) and chronic obstructive pulmonary disease (COPD) is one fraught with the risk of PE recurrence, and fatal outcome, respectively [1], the association of the two disorders is one that should have merited some mention in the review of heightened long term cardiovascular risk after exacerbations of COPD [2], notwithstanding the uncertainty about the true prevalence of PE in patients with COPD [3],[4] . The uncertainty about PE prevalence in COPD is, arguably, in part, attributable to the fact that some COPD patients have coexisting carcinomatosis as a risk factor for PE in its own right [3]. In a systematic review and meta-analysis published in 2009, Rizkallah et al documented a PE prevalence amounting to 19.9%(95% Confidence Interval 6.7% to 33%) among patients with acute exacerbations of COPD[4]. Anecdotal reports also document the association of right heart thrombi (one of the stigmata of pulmonary thromboembolism) and COPD [5-8].
Over and above its association with PE, COPD also appears to be a risk factor for the occurrence of "in situ" thrombosis in the pulmonary arterial vasculature [9],[10], a development which is a long term risk factor for right heart failure.
Arguably, in view of the prothrombotic environment generated by acute exacerbations of COPD, and the fact that atrial fibrillation might be prevalent in approximately 15% of COPD patients [2], there might be a case for including COPD as one of the parameters in the CHA2DS2Vasc risk assessment formula, so as to generate a rational basis for initiating long-term anticoagulant therapy in patients who have the association of COPD and atrial fibrillation.
For all these reasons all aspects of the relationship between COPD and pulmonary thromboembolism should be the subject of vigilant documentation , verification, and evaluation for long term cardiovascular risk.
I have no conflict of interest.
References
Bertoletti L., Quenet S., Laporte S et al
Pulmonary embolism and 3-month outcomes in 4035 patients with venous thromboembolism and chronic obstructive pulmonary disease: data from RIETE Registry
Respiratory Research 2013;14:75
doi 10.1186/1465-9921-14-75
[2] Hawkins NB., Nordon C., Rhodes K et al
Heightened long term cardiovascular risk after exacerbations of chronic obstructive pulmonary disease
HEART
Epub ahead of print doi:10.1136/heartjnl-2023-323487
[3] Tillie-Leblond I., Marquette C-H., Perez T et al
Pulmonary embolism in patients with unexplained exacerbations of chronic obstructive pulmonary disease: Prevalence and risk factors
Ann Intern Med 2006;144:390-396
[4]Rizkallah J ., Man P., Sin DD
Prevalence of pulmonary embolism in acute exacerbations of COPD
A systematic review and meta-analysis
CHEST 2009;135:786-793
[5] Noji Y., Kojima T., Aoyama T
Free-floating thrombus in right heart and massive pulmonary embolism migrating into pulmonary artery
CIRCULATION 2005;111:e438-e439
[6] Ates BA., Esenboga K., Ozyuncu N
Isolated right ventricular thrombus with severe chronic obstructive pulmonary disease
Journal of Cardiology and Cardiovascular Surgery 2023;1:14-15
[7] Gur H., Keren G., Levo Y
Right ventricular thrombus and pulmonary emboli in a patient with emphysema. An echocardiographic and doppler documentation
Clin Cardiol 1987;10:680-682
[8] Hosna AU., Miller D., Makhoul K., Noff N
SA case of chronic pulmonary embolism resulting in pulmonary hypertension and decompensated right heart failure
CUREUS 2022;14:e32771
doi 10.7759/cureus 32771
[9] Wang C., Du M., Cao D
A pathological study of in situ thrombosis of small pulmonary arteries and arterioles in autopsy cases pf chronic cor pulmonale
Zhaonghua Yi Xue Za Zhi 1997;77:123-125
Article in Chines: Abstract in English
[10] Russo A., De Uca M., Vigna C et al
Central pulmonary artery lesions in chronic obstructive pulmonary disease
CIRCULATION 1999;100: 1808-1815
The data was evaluated by the authors using Fine-Gray competing risk models, with C-19 linked deaths included as competing risks. In the text, they referred to this as "To account for the competing risk of death associated with COVID-19."
When examining the cardiovascular and thromboembolic effects of COVID-19, it is not appropriate to consider COVID-19 associated mortality as a competing risk. Furthermore, these consequences are the primary factors contributing to mortality in cases of C-19 infection.
In their analysis of population-based mortality from dissecting aortic aneurysm(DAA), the authors drew attention to the need for further research to be undertaken to optimise earlier identification of those at risk[1]. Relevant to this task is the increasing awareness of the entity of COVID-19-related aortitis, and the documentation of increasing numbers of anecdotal reports of the association of COVID-19 infection and DAA.
The report by Shergall et al was one of the first to show a persuasively valid causal relationship between COVID-19 infection and aortitis. In that example a 71 year old man presented with chest pain radiating to the scapula, within a few days of experiencing symptomatic COVID-19 infection. Although, by this time, the nasopharyngeal swab test was negative for COVID-19, he had serological evidence of recent COVID-19 infection. Computed tomography showed evidence of diffuse inflammatory aortitis. Following a course of prednisolone 40 mg/day, subsequent tomography showed partial resolution of the aortitis[2].
In three subsequent reports, it was the occurrence of DAA(presumably as a complication of aortitis) , rather than aortitis per se, which was the issue of concern, especially because of the pain-free nature of the clinical presentation.
In one of those patients , a 45 year old previously healthy non-smoker with no comorbidities, the only symptoms comprised a 3 days history of fever, cough, and dyspnoea. He had neither...
In their analysis of population-based mortality from dissecting aortic aneurysm(DAA), the authors drew attention to the need for further research to be undertaken to optimise earlier identification of those at risk[1]. Relevant to this task is the increasing awareness of the entity of COVID-19-related aortitis, and the documentation of increasing numbers of anecdotal reports of the association of COVID-19 infection and DAA.
The report by Shergall et al was one of the first to show a persuasively valid causal relationship between COVID-19 infection and aortitis. In that example a 71 year old man presented with chest pain radiating to the scapula, within a few days of experiencing symptomatic COVID-19 infection. Although, by this time, the nasopharyngeal swab test was negative for COVID-19, he had serological evidence of recent COVID-19 infection. Computed tomography showed evidence of diffuse inflammatory aortitis. Following a course of prednisolone 40 mg/day, subsequent tomography showed partial resolution of the aortitis[2].
In three subsequent reports, it was the occurrence of DAA(presumably as a complication of aortitis) , rather than aortitis per se, which was the issue of concern, especially because of the pain-free nature of the clinical presentation.
In one of those patients , a 45 year old previously healthy non-smoker with no comorbidities, the only symptoms comprised a 3 days history of fever, cough, and dyspnoea. He had neither chest pain nor back pain.. The reverse transcriptase test for SARS-2 CoV-2 was positive. Computed tomography showed typical ground glass opacification in the lung fields, and, unexpectedly, also showed DAA[3].
Two other patients, aged 42 and 55, respectively, with proven COVID-19 infection , also experienced a pain-free presentation of DAA[4],[5].
Aortitis has also been reported as a complication of the administration of the BNT162b2 vaccine. In this instance aortitis occurred in association with vaccine-related pericarditis. Aortitis was complicated by the subsequent development of fatal DAA[6].
In their systematic review of the association of COVID-19 and DAA, Ramandi et al commented that the level of Van Willebrand Factor appeared to show an increase in COVID-19-infected patients. They postulated that this was indicative of extensive endothelial activation[7].
These observations raise the question"Is COVID-19 the new atherosclerosis?"[8]. This question was posed in the context of yet another report of the association of COVID-19 and DAA[8].
If it were the case that both COVID-19 and vaccination could be risk factors for aortitis and, hence, aortic dissection, there is a potential for a huge upsurge in DAA prevalence and incidence following the COVID-19 pandemic. This upsurge could be monitored by evaluating the prevalence of aortitis in patience with long COVID, the latter presumably a disorder in which there is a continuous background of COVID-19-related activity arguably involving varying degrees of proinflammatory cytokine activity. Imaging studies for identification of aortitis could go hand in hand with evaluation of Von Willebrand Factor. Those strategies for quantifying background prevalence of COVID-19-related aortitis might give some indication of whether or not previous COVID-19 infection is a substantial risk factor for DAA.
I have no conflict of interest
References
[1] Hamilton BCS and Eagle KA
Winning the battle but losing the war: increased population-based mortality from aortic dissection
Heart 2023;doi:10.1136/heartjnl-2023-323302
[2]Shergill S., Davies J., Bloomfield J
Florid aortitis following SARS-CoV-2 infection
Eur Heart J 2020;41:4286
[3]Jariwala P., Kambie R., Sridhar S., Mishra KC., Jadhav KP
A fatal association of COVID-19 and acute complicated Type B aortic dissection
Interventional management in a difficult situation
IHJ Cardiovascular Case Reports 2021;5:94-97
[4] Alrjoob M., Alkhatib A., Khan AM et al
COVID-19 It's not over yet:A case of COVID-19-induced aortitis complicated by aortic dissection
CHEST 2023
DOI.org/10.1016/j.chest.2023.07.232
[5]Gebril A., Nawaz A., Ashour S., Nasr MK., Eebelihy OE
Silent Type B aortic dissection accidentally discovered in a COVID-19-positive patient
CUREUS 2023;15:e41373 DOI:10.7759/cureus.41373
[6]Takahashi M., Kondo T., Yamasaki G et al
An autopsy case report of aortic dissection complicated with histiolymphocytic pericarditis and aortic inflammation after m RNA Covid-19 vaccination
Legal Medicine 2022;59:102154
[7] Ramandi A., Akbarzadeh M., Khaheshi I., Khalilian MR
Aortic dissection and COVID-19: A comprehensive systematic review
Curr Probl Cardiol 2023;48:101129
[8] Vergopoulos S., Evalgeliou A., Boulmpou A et al
Acute aortic dissection Type A in the early period after COVID-19 infection
HSOA Journal of Angiology & Vascular Surgery 2022;7:085
DOI:10.24966/AVS-7397/100085
[9] Ahamed J., Laurence J
Long covid endotheliopathy: hypthesized mechanisms and potential therapeutic approaches
J Clin Invest 2022;132;e161167
doi;10.1172/JCI161167
The analysis of aetiology, ejection fraction, and mortality in heart failure is one which would benefit from inclusion of constrictive pericarditis(CP) as the differential diagnosis of some of the underlying causes of congestive heart failure(CHF) enumerated by Fritz et al[1].
The rationale is that some of the underlying causes of CP, such as radiotherapy[2], tuberculosis, sarcoidosis, and Whipple's disease are also causes of myocarditis and, hence, CHF[3]. Conversely, CP might, itself, be a cause of atrophy of myocardial fibres, a state of affairs "which probably occurs in response to ischemia owing to cardiac compression[4]. CP-related myocardial dysfunction is more likely to occur when aetiologies of CP such as radiation therapy, cardiac surgery, and systemic inflammatory diseases are operative[4].
It is, therefore, likely that the echocardiographic documentation of left ventricular ejection fraction(LVEF) amounting to < 50% in a substantial minority of CP patients[5],[6],[7] might be attributable to coexistence of CP and left ventricular systolic dysfunction, a state of affairs that might make CP clinically and echocardiographically indistinguishable from dilated cardiomyopathy. Conversely, left ventricular diastolic dysfunction might predominate, and the clinical manifestations of CP characterised by LVEF > 50% may be indistinguishable from the clinical manifestations of, for example, restrictive cardiomyopathy[8].
Among 43...
The analysis of aetiology, ejection fraction, and mortality in heart failure is one which would benefit from inclusion of constrictive pericarditis(CP) as the differential diagnosis of some of the underlying causes of congestive heart failure(CHF) enumerated by Fritz et al[1].
The rationale is that some of the underlying causes of CP, such as radiotherapy[2], tuberculosis, sarcoidosis, and Whipple's disease are also causes of myocarditis and, hence, CHF[3]. Conversely, CP might, itself, be a cause of atrophy of myocardial fibres, a state of affairs "which probably occurs in response to ischemia owing to cardiac compression[4]. CP-related myocardial dysfunction is more likely to occur when aetiologies of CP such as radiation therapy, cardiac surgery, and systemic inflammatory diseases are operative[4].
It is, therefore, likely that the echocardiographic documentation of left ventricular ejection fraction(LVEF) amounting to < 50% in a substantial minority of CP patients[5],[6],[7] might be attributable to coexistence of CP and left ventricular systolic dysfunction, a state of affairs that might make CP clinically and echocardiographically indistinguishable from dilated cardiomyopathy. Conversely, left ventricular diastolic dysfunction might predominate, and the clinical manifestations of CP characterised by LVEF > 50% may be indistinguishable from the clinical manifestations of, for example, restrictive cardiomyopathy[8].
Among 43 CP patients evaluated by Oreto et al, nine(20.9%) had LVEF < 40%. . Brain Natriuretic Peptide levels(inter quatrile range) ranged from 114 pg/ml-782 pg/ml[5]. Among 140 CP patients evaluated by Porta-Sanchez et al, twenty eight(20%) had LVEF less than or equal to 50%. There was no documentation of concomitant BNP values[6]. Among 97% CP patients evaluated by Busch et al , three(3.1%) had LVEF < 30%, twenty-three (23.7%) had LVEF 31%-55%, and seventy-one(72.2%) had LVEF > 56%. There was no documentation of concomitant BNP data[7]. When 6 CP patients , each with LVEF amounting to 60%, were compared with 5 patients with restrictive cardiomyopathy(RCMP), in whom LVEF amounted to 30%, 40%, 55%, 60% and 60%, respectively, BNP ranged from 50 pg/ml to 186 pg/ml in the CP subgroup versus 639 pg/ml to 1,060 pg/ml in the RCMP subgroup[8]. All patients, both in the CP subgroup and in the RCMP subgroup, were in New York Heart Association functional class III or IV[8]. Accordingly, the differential diagnosis of the association of symptomatic CHF and normal or only marginally elevated BNP levels should include, not only heart failure with preserved ejection fraction, even in the absence of a specific diagnosis of RCMP, as was the case in 46 subjects with clinically overt CHF who were characterised by pulmonary capillary wedge pressure > 15 mm Hg,[9], but, also, CP[8].
In conclusion, given the considerable overlap in clinical features and in BNP levels between the subgroups of CHF patients evaluated by Fritz et al[1] and the subgoups of patients I have enumerated[5-9], a mediation analysis can only be complete if the evaluation also includes CP patients with LVEF ranging from <40% to > 50%, and the corresponding range of BNP values. A comprehensive and detailed evaluation along those lines has not yet been done although it is long overdue, given the fact that CP , when diagnosed early, is an eminently reversible underlying cause of CHF[4].
I have no conflict of interest
References
[1] Fritz J., Belovari K., Ulmer H et al
Aetiology, ejection fraction, and mortality in chronic heart failure: a mediation analysis
Heart E pub ahead of print
DOI:10.1136/heartjnl-2023-322803
[2]Saiki H., Petersen IA., Scott CG et al
Risk of heart failure with preserved ejection fraction in older women after contemporary radiotherapy for breast caner
Circulation 2017;135:1388-1396
[3] Jolobe, OMP
High-risk and low prevalence disease: Cardiac sarcoidosis and some of its mimics
IJC Heart & Vasculature 2023;47:101221
doi.org/10.1016/j.ijcha.2023.101221
[4]Syed FF., Schaff HV., Oh JK
Constrictive pericarditis: a curable diastolic heart failure
Nat Rev Cardiol 20114;11:530-544
[5] Oreto L., Mayer A., Todaro MC et al
Contemporary clinical spectrum of constrictive pericarditis: a 10 year experience
International Journal of Cardiology 2013;163:339-341
[6] Porta-Sanchez A., Sagrista-Sauleda J., Ferreira-Gonzalez I et al
Constrictive pericarditis. Etiologic spectrum, patterns of clinical presentation, prognostic factors, and long-term follow up
Rev Esp Cardiol 2015;68:1092-1100
[7] Busch C., Penov K., Amorim PA et al
Risk factors for mortality after pericardiectomy for chronic constrictive pericarditis in a large single-centre cohort
European Journal of Cardio-Thoracic Surgery 2015;48:e110-e116
[8]Leya FS., Arab D., Joyal D et al
The efficacy of brain natriuretic peptide levels in differentiating constrictive pericarditis from restrictive cardiomyopathy
JACC 2005;45:1900-1902.
[9]Anjan VY., Loftus TH., Burke MA et al
Prevalence, clinical phenotype, and outcomes associated with normal B type natriuretic peptide levels in heart failure with preserved ejection fraction
Am J Cardiol 2012;110:870-875
Over and above the scenario cited by the authors, where the presence of Roth spots became a "red flag" for infective endocarditis(IE)[1], clinicians also need to take note of endogenous endophthalmitis as a "red flag" for IE, both in the context of native valve IE, and in the context of intracardiac device-related IE.
Endophthalmitis and native valve infective endocarditis:-
Awareness of endophthalmitis as a manifestation of IE is of heightened value when IE presents in the absence of a cardiac murmur, so-called "silent" infective endocarditis. In one patient with silent IE , Roth spots were identified in the same eye that was affected by endogenous endophthalmitis[2]. In another patient with silent IE initial transthoracic echocardiography(TTE) did not disclose any vegetations. Ten days later, however, transoesophageal echocardiography(TOE) disclosed the presence of vegetations[3]. The clinical course of another patient with silent IE was characterised by non diagnostic initial TTE, and nondiagnostic TOE on day 12. On day 31, however, TOE showed severe aortic regurgitation and what appeared to be a vegetation on the aortic valve. Intraoperatively, however, what had previously appeared to be a vegetation proved to be a destroyed non coronary valve tip[4].
Endophthalmitis and infective endocarditis attributable to intracardiac devices:-
Endogenous endophthalmitis is also a red flag for infective endocarditis attr...
Over and above the scenario cited by the authors, where the presence of Roth spots became a "red flag" for infective endocarditis(IE)[1], clinicians also need to take note of endogenous endophthalmitis as a "red flag" for IE, both in the context of native valve IE, and in the context of intracardiac device-related IE.
Endophthalmitis and native valve infective endocarditis:-
Awareness of endophthalmitis as a manifestation of IE is of heightened value when IE presents in the absence of a cardiac murmur, so-called "silent" infective endocarditis. In one patient with silent IE , Roth spots were identified in the same eye that was affected by endogenous endophthalmitis[2]. In another patient with silent IE initial transthoracic echocardiography(TTE) did not disclose any vegetations. Ten days later, however, transoesophageal echocardiography(TOE) disclosed the presence of vegetations[3]. The clinical course of another patient with silent IE was characterised by non diagnostic initial TTE, and nondiagnostic TOE on day 12. On day 31, however, TOE showed severe aortic regurgitation and what appeared to be a vegetation on the aortic valve. Intraoperatively, however, what had previously appeared to be a vegetation proved to be a destroyed non coronary valve tip[4].
Endophthalmitis and infective endocarditis attributable to intracardiac devices:-
Endogenous endophthalmitis is also a red flag for infective endocarditis attributable to intracardiac devices such as permanent pacemekers and implantable cardioverter defibrillators. The diagnosis of device-related IE comes to mind most readily when the patient has concurrent inflammatory signs of of infection of the device pocket[5]. Regardless of presence or absence of signs of device pocket infection , however, the presence of endogenous endophthalmitis should, also, raise the index of suspicion for device -related IE, especially when stigmata of septic pulmonary embolism are also present[6]. In the latter example, where no mention was made of the appearance of the device pocket, TOE showed a 20 mm mobile vegetation attached to the right atrial lead[6]. The association of endophthalmitis, pulmonary consolidation(with or without cavitation) , and hypotension(the latter attributable to systemic sepsis), is a "triad" that should raise the index of suspicion for device-related IE[7].
Echocardiography expedites the workup of suspected intracardiac device-related IE. TOE has greater sensitivity than TTE for identifying vegetations on the leads and for identifying vegetations on the heart valves. Accordingly, TOE can be offered as the first echocardiographic test if clinical suspicion is sufficiently high[8]. Nuclear imaging, using 18 Fluoro Deoxy Glucose positron emission tomography computed tomography is highly specific for lead endocarditis given the fact that, unlike TOE, it can also distinguish between infected thrombi and uninfected thrombi attached to the leads[8]. Sensitivity is however, suboptimal, given the the negative results believed to be attributable to previous antibiotic therapy or attributable to vegetation size being lower than the spatial resolution of nuclear imaging[9].
A comprehensive account of best practice in the work up of suspected device-related IE was made by Dilsizian et al[8].
I have no conflict of interest.
References
[1]Ng JY., Zarook E., Nicholson L et al
Eyes and the heart: what a clinician should know
Heart 2023
Epub ahead of print
DOI 10.1136/heartjnl-2022-322081
[2]Carmelli G., Surles T., Brown A
Endophthalmitis and myocotic aneurysm: The only clues to underlying endocarditis
Clin Pract Cases Emerg Med 2018 https://doi.org/10.5811/cpcem.2017.8.34723
[3]Sim YR., Lee YJ., Park SW et al
Infective endocarditis presenting as endogenous endophthalmitis secondary to streptococcus agalactiae in a healthy adult
CSE Rep Literat Rev Infect Chemother 2017;49:286-292
[4]Nakata M., Mashidori T., Higa N et al
Infective endocarditis with no underlying disease for which bacterial endophthalmitis have been first symptom
Intern Med 2020;59:2061-2065
[5]Looser PM., Saleh L., Thomas G., Cheung JW
Systemic infection due to subcutaneous implantable cardioverter defibrillator implantation: Importance of early recognition and treatment of device pocket related complications
Heart Rhythm Case Reports 2017;3:40-42
[6] Patel N., McDonald ML., Bradford NS et al
AngioVac debulking in endocarditis patients with large, device-related vegetations
The Journal of Innovations in Cardiac Rhythm Management 2018;9:3291-3296
[7]Sarvat B., Sarria JC
Implantable cardioverter-defibrillator infection due to Scetosporium apiospermum
Journal of Infection 2007;55:e109-e113
[8]Dilsizian V., Budde RPJ., Chen W et al
Best practice for imaging cardiac device-related infections and endocarditis
A JACC Cardiovascular imaging expert panel statement
JACC Cardiovascular Imaging 2022;15:891-911
[9]Cautela J., Alessandrini S., Carmmiller S et al
Diagnostic yield of FDG positron emission tomography/computed tomography in patients with CEID infection: a pilot study
Europace 2013;15:252-257
Dear Sir,
we read with deep interest the paper by Marcadé-Besora[1] and collaborators, providing extremely reliable evidence in favour of a long-term protective effect of SARS-CoV-2 vaccination, against cardiovascular events (especially thrombosis-related ones), in patients recovering from an acute SARS-CoV-2 infection.
Such protective affect remains significant up to one year after acute infection, and this not only indirectly confirms that the well-recognized thrombophylic disturbance associated to SARS-CoV-2 lasts actually longer than initially thought[2], but also suggests that this is - at least in part - preventable, through immune mechanisms.
In the study, the follow-up ended on the first post-COVID outcome event, so occasional SARS-CoV-2 reinfections, occurring more often in the unvaccinated individuals, cannot be the reason for the observed differences between groups.
The authors did not stratify results according to the number of vaccine doses received: we suggest this analysis to be done. In fact, viral neutralization efficacy conferred by COVID vaccines is not “all-nothing” and depends on time since last booster and on number of doses received[3]: should the cardiovascular protective effect observed by the authors follow the same pattern, this would add a strong evidence in favour of its linkage to vaccination, instead of other potentially associated confounders.
In a different setting, and a much smaller scale, we also obs...
Show MoreA trial of loop diuretic therapy in patients who have not received the benefit of evaluation either by echocardiography or by natriuretic peptide testing can be an opportunity to maximise alternative strategies for validating the diagnosis of congestive heart failure(CHF)
Show MoreThe following are some of the alternative strategies:-
(1)Evaluation of jugular venous pressure(JVP).
This strategy was poorly maximised in the anecdotal report of two patients(patient 2 and patient 3) ,with peripheral oedema and breathlessness, in whom the initial cardiovascular examination was recorded as "normal". A subsequent repeat clinical examination revealed an extremely elevated JVP attributable to constrictive pericarditis[1].
Documentation of body weight before and after a trial of loop diuretic treatment enhances the diagnostic value of evaluation of JVP. The rationale is that a JVP that is persistently high in spite of significant weight loss after diuretic use can be a powerful indicator of the diagnosis of constrictive pericarditis[2]]
(ii) Documentation of a fall in forced vital capacity(FVC) after a trial of loop diuretic treatment.
In that context, a fall in body weight which is accompanied by a fall in FVC after a trial of loop diuretic treatment is indicative of a reversible restrictive ventilatory defect that is attributable to pulmonary congestion and, hence, CHF. Reversibility of FVC after loop diuretics is a well document...
The assertion that natriuretic peptide levels below a defined threshold(for, example, Brain Natriuretic Peptide(BNP) levels < 100 pg/mL) can safely rule out heart failure and may also obviate the need to proceed to early echocardiography[1] should be qualified as follows:-
Show MoreEarly echocardiography does not necessarily confirm or refute the diagnosis of congestive heart failure(CHF) in patients with heart failure characterised by preserved ejection fraction(HFpEF). This is a truism that ought to be valid even in HFpEF patients with BNP levels < 100 pg/mL[2]. In the latter study , among 159 patients who had been hospitalised for CHF, the latter characterised by left ventricular ejection fraction(LVEF) amounting to >50%, in association with pulmonary capillary wedge pressure > 15 mm Hg, 46/159 patients(29%) had BNP equal to or less than 100 pg/mL[2].. Accordingly, if the index of suspicion for CHF is sufficiently high strategies other than echocardiography should be deployed to confirm or refute the diagnosis of CHF. The following are some of those strategies:-
(i) Clinical evaluation of jugular venous pressure(JVP). A raised JVP is indicative of a right atrial pressure beyond the normal upper limit of 8 mm Hg[3]. Furthermore, jugular venous distension is associated with a likelihood ratio amounting to 5.1(95% Confidence Interval, 3.2 to 7.9) in favour of a diagnosis of CHF[4].
(ii)Evaluation of inferior vena cava(IVC) diameter. An...
Notwithstanding the assertion that the N-terminal pro-BNP-type natriuretic peptide(NT-proBNP) is highly sensitive and has excellent negative predictive value for heart failure(HF)[1], the following caveats may apply:-
Show MoreFirstly, the negative predictive value of NT-pro BNP is severely curtailed in HF patients who are obese(BMI 30.0 or more), with the consequence that low blood levels of that biomarker do not rule out a diagnosis of HF with preserved ejection fraction(HFpEF)[2]. In the latter study there were 30 patients with left ventricular ejection fraction of 50% or more who had complied with the European Society of Cardiology diagnostic criteria for HF. Twenty nine of the patients had a Body Mass Index(BMI) of 30.0 or more, and one had a BMI of 27(ie oeversight but not obese). Fifteen of the patients had NT-proBNP levels amounting to < 125 pg/ml[2]
In the absence of the confounding effect of obesity, levels of NT-pro BNP below the diagnostic cut off level of 400 pg/ml also appear to be more prevalent in HFpEF patients than in patients with heart failure with reduced ejection fraction(HFrEF) [3]. In the latter study a comparison was made between 65 HFpEF patients and 50 patients with HFrEF. Mean values for BMI amounted to 24 in both subgroups. Criteria for HFpEF comprised symptoms of HF in association with echocardiographic documentation of an E/A ratio < 1 and left ventricular ejection fraction(LVEF) of 50% or more.. Criteria for HFr...
Notwithstanding the fact that Blagova et al did not identify any specific findings related to eosinophilic myocarditis(EM) in their series of 14 patients with post-COVID myoendocarditis[1], anecdotal reports not cited by Techasatian et al[2] have documented an association between COVID 19 infection and eosinophilic myocarditis[3-5].
Show MoreCraver et al reported the case of a previously healthy 17 year old male who had a 2 day history of headache, nausea and vomiting , followed by sudden death. At autopsy his heart weighed 500 grams(expected weight fro age was 262-295 grams), with a histological profile characterised by an inflammatory infiltrate which had prominent" eosinophils, in addition to lymphocytes and macrophages. This was associated with multiple foci of myocyte necrosis.. Histological examination of the lungs revealed mild chronic inflammation of the bronchi with only occasional eosinophils. Postmortem nasopharyngeal swabs tested positive for SARS-2 CoV-2[3].
In two other cases of the association of COVID-19 infection and eosinophilic myocarditis, each of the patients[4],[5] had a previous history of chronic asthma, thereby raising the possibility that eosinophilic myocarditis might have been a manifestation of eosinophilic granulomatosis with polyangiitis.
However, given the fact that, in its own right, COVID-19 infection can be a trigger for eosinophilic pneumonia[6], the association of eosinophilic myocarditis and COVID-19 infectio...
In view of the fact that the association of pulmonary embolism (PE) and chronic obstructive pulmonary disease (COPD) is one fraught with the risk of PE recurrence, and fatal outcome, respectively [1], the association of the two disorders is one that should have merited some mention in the review of heightened long term cardiovascular risk after exacerbations of COPD [2], notwithstanding the uncertainty about the true prevalence of PE in patients with COPD [3],[4] . The uncertainty about PE prevalence in COPD is, arguably, in part, attributable to the fact that some COPD patients have coexisting carcinomatosis as a risk factor for PE in its own right [3]. In a systematic review and meta-analysis published in 2009, Rizkallah et al documented a PE prevalence amounting to 19.9%(95% Confidence Interval 6.7% to 33%) among patients with acute exacerbations of COPD[4]. Anecdotal reports also document the association of right heart thrombi (one of the stigmata of pulmonary thromboembolism) and COPD [5-8].
Show MoreOver and above its association with PE, COPD also appears to be a risk factor for the occurrence of "in situ" thrombosis in the pulmonary arterial vasculature [9],[10], a development which is a long term risk factor for right heart failure.
Arguably, in view of the prothrombotic environment generated by acute exacerbations of COPD, and the fact that atrial fibrillation might be prevalent in approximately 15% of COPD patients [2], there might b...
The data was evaluated by the authors using Fine-Gray competing risk models, with C-19 linked deaths included as competing risks. In the text, they referred to this as "To account for the competing risk of death associated with COVID-19."
When examining the cardiovascular and thromboembolic effects of COVID-19, it is not appropriate to consider COVID-19 associated mortality as a competing risk. Furthermore, these consequences are the primary factors contributing to mortality in cases of C-19 infection.
In their analysis of population-based mortality from dissecting aortic aneurysm(DAA), the authors drew attention to the need for further research to be undertaken to optimise earlier identification of those at risk[1]. Relevant to this task is the increasing awareness of the entity of COVID-19-related aortitis, and the documentation of increasing numbers of anecdotal reports of the association of COVID-19 infection and DAA.
Show MoreThe report by Shergall et al was one of the first to show a persuasively valid causal relationship between COVID-19 infection and aortitis. In that example a 71 year old man presented with chest pain radiating to the scapula, within a few days of experiencing symptomatic COVID-19 infection. Although, by this time, the nasopharyngeal swab test was negative for COVID-19, he had serological evidence of recent COVID-19 infection. Computed tomography showed evidence of diffuse inflammatory aortitis. Following a course of prednisolone 40 mg/day, subsequent tomography showed partial resolution of the aortitis[2].
In three subsequent reports, it was the occurrence of DAA(presumably as a complication of aortitis) , rather than aortitis per se, which was the issue of concern, especially because of the pain-free nature of the clinical presentation.
In one of those patients , a 45 year old previously healthy non-smoker with no comorbidities, the only symptoms comprised a 3 days history of fever, cough, and dyspnoea. He had neither...
The analysis of aetiology, ejection fraction, and mortality in heart failure is one which would benefit from inclusion of constrictive pericarditis(CP) as the differential diagnosis of some of the underlying causes of congestive heart failure(CHF) enumerated by Fritz et al[1].
Show MoreThe rationale is that some of the underlying causes of CP, such as radiotherapy[2], tuberculosis, sarcoidosis, and Whipple's disease are also causes of myocarditis and, hence, CHF[3]. Conversely, CP might, itself, be a cause of atrophy of myocardial fibres, a state of affairs "which probably occurs in response to ischemia owing to cardiac compression[4]. CP-related myocardial dysfunction is more likely to occur when aetiologies of CP such as radiation therapy, cardiac surgery, and systemic inflammatory diseases are operative[4].
It is, therefore, likely that the echocardiographic documentation of left ventricular ejection fraction(LVEF) amounting to < 50% in a substantial minority of CP patients[5],[6],[7] might be attributable to coexistence of CP and left ventricular systolic dysfunction, a state of affairs that might make CP clinically and echocardiographically indistinguishable from dilated cardiomyopathy. Conversely, left ventricular diastolic dysfunction might predominate, and the clinical manifestations of CP characterised by LVEF > 50% may be indistinguishable from the clinical manifestations of, for example, restrictive cardiomyopathy[8].
Among 43...
Over and above the scenario cited by the authors, where the presence of Roth spots became a "red flag" for infective endocarditis(IE)[1], clinicians also need to take note of endogenous endophthalmitis as a "red flag" for IE, both in the context of native valve IE, and in the context of intracardiac device-related IE.
Endophthalmitis and native valve infective endocarditis:-
Awareness of endophthalmitis as a manifestation of IE is of heightened value when IE presents in the absence of a cardiac murmur, so-called "silent" infective endocarditis. In one patient with silent IE , Roth spots were identified in the same eye that was affected by endogenous endophthalmitis[2]. In another patient with silent IE initial transthoracic echocardiography(TTE) did not disclose any vegetations. Ten days later, however, transoesophageal echocardiography(TOE) disclosed the presence of vegetations[3]. The clinical course of another patient with silent IE was characterised by non diagnostic initial TTE, and nondiagnostic TOE on day 12. On day 31, however, TOE showed severe aortic regurgitation and what appeared to be a vegetation on the aortic valve. Intraoperatively, however, what had previously appeared to be a vegetation proved to be a destroyed non coronary valve tip[4].
Endophthalmitis and infective endocarditis attributable to intracardiac devices:-
Endogenous endophthalmitis is also a red flag for infective endocarditis attr...
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