Intriguingly, in the recent study, severe mitral regurgitation was present in as many as 10.3% of patients who did not have left ventricular outflow tract obstruction(LVOTO)[1]. This observation raises the question of whether or not mitral regurgitation(MR) might, in some of those cases, have been attributable to Takotsubo-related tethering of the mitral valve leaflets[2]. The latter was the underlying cause of severe MR in a 57 year old woman with previous history of treated hypertension who presented with chest pain and a blood pressure of 119/84 mm Hg. What we do not know is whether or not that blood pressure was her usual "on treatment" blood pressure or whether it represented a significant fall from her usual blood pressure. Her electocardiogram(ECG) showed ST segment elevation in leads V5 and V6. Coronary angiography did not show any obstructive lesion. Instead, she had stigmata of TTC, namely, apical left ventricular apical hypokinesis and basal hyperkinesis. Furthermore, she had eccentric mitral regurgitation associated with tethering of the anterior mitral leaflet. Neither LVOTO nor systolic anterior motion(SAM) of the mitral valve was observed. Her left ventricular ejection fraction(LVEF) amounted to 59.7%. After an uneventful clinical course she had a follow up which showed complete resolution of MR[2]. Leaflet tethering is believed also to be implicated in the aetiopathogenesis of TTC-related tricuspid regurgitation(TR)[3]. On occasions...
Intriguingly, in the recent study, severe mitral regurgitation was present in as many as 10.3% of patients who did not have left ventricular outflow tract obstruction(LVOTO)[1]. This observation raises the question of whether or not mitral regurgitation(MR) might, in some of those cases, have been attributable to Takotsubo-related tethering of the mitral valve leaflets[2]. The latter was the underlying cause of severe MR in a 57 year old woman with previous history of treated hypertension who presented with chest pain and a blood pressure of 119/84 mm Hg. What we do not know is whether or not that blood pressure was her usual "on treatment" blood pressure or whether it represented a significant fall from her usual blood pressure. Her electocardiogram(ECG) showed ST segment elevation in leads V5 and V6. Coronary angiography did not show any obstructive lesion. Instead, she had stigmata of TTC, namely, apical left ventricular apical hypokinesis and basal hyperkinesis. Furthermore, she had eccentric mitral regurgitation associated with tethering of the anterior mitral leaflet. Neither LVOTO nor systolic anterior motion(SAM) of the mitral valve was observed. Her left ventricular ejection fraction(LVEF) amounted to 59.7%. After an uneventful clinical course she had a follow up which showed complete resolution of MR[2]. Leaflet tethering is believed also to be implicated in the aetiopathogenesis of TTC-related tricuspid regurgitation(TR)[3]. On occasions moderately severe TTC-related TR may coexist with moderately severe TTC-related MR[4].
Severe MR can also be a manifestation of the coexistence of TTC and hitherto unrecognised hypertrophic obstructive cardiomyopathy(HOCUM)[5] In the latter example the patient presented with hypotension, and the echocardiogram showed apical hypokinesia and "massive" MR associated with SAM of the mitral valve. Dynamic left ventricular outflow tract gradient amounted to 250 mm Hg. Endomyocardial biopsy showed hypertrophied and bizarre myocytes with myocyte disarray, in addition to histological changes often documented in TTC[5]
In the presence of cardiogenic shock the differential diagnosis of MR also includes TTC-related papillary muscle rupture(PMR)[6],[7],[8]. Paradoxically, in one case, despite the presence of hypotension(blood pressure 90/50 mm Hg) and heart rate of 160/minute, echocardiography only showed mild to moderate MR. Nevertheless PMR was documented, in addition to apical hypokinesia and basal hyperkinesis. LVEF amounted to 20%, and no stenosis was documented on coronary angiography. The patient was managed with dobutamine and diuretics, followed by surgical repair of the mitral valve apparatus. Initial management with vasoppressors was also deployed in a 36 year old woman with PMR giving rise to flail posterior mitral leaflet[7]. In Yaghoubi et al a 36 year old woman presented without any ST segment changes, even after recovery from a cardiac arrest. Echocardiography showed severe MR and mid to distal left ventricular hypokinesia. Coronary angiography did not show any abnormality.. Surgical intervention disclosed rupture of the chordae tendinae group of the anterior papillary muscle[8].
References
I have no conflict of interest.
References
[1]Villa-Sanjuan S., Nunez-Gil IJ., Vedia O et al
Left ventricular outflow tract obstruction in Takotsubo syndrome with cardiogenic shock prognosis and treatment
Heart 2024;Epub ahead of print
[2]Nonala D., Takase H., Machii M., Ohno K
Intraventricular thrombus and severe mitral regurgitation in the acute phase of takotsubo cardiomyopathy: two case reports
Journal of Medical Case Reports 2029;13: 152
[3]Sumida H., Morihisa K., Katahira K et al
Isolated right ventricular stress(Takotsubo) cardiomyopathy
Internal Medicine 2017;56:2159-2164
[4]Lee WLS., Li-fu M., Chan HWR., Chen M-z
Takotsubo syndrome with transient complete atrioventricular block
Chinese Medical Journal 2006;
[5]Arakawa K., Gondo T., Matsushita K et al
Takotsubo cardiomyopathy in a patient with previously undiagnosed hyperterophic cardiomyopathy with latent obstruction
Intern Med 2018;57:2969-2973
[6]Nef HM., Mollmann H., Hilpert P et al
Severe mitral regurgitation in Tako-Tsubo cardiomyopathy
Int J Cardiol 2009;132:e77-e78
[7]Chen D., Abi-Hanna D., Lambros J
Rupture of s broken heart: A rare cause of acute mitral regurgitation due to papillary muscle rupture complicating Takotsubo cardiomyopathy
Eur Heart J Cardiovascular Imaging 2020;21:suppl(1 P 1297)
[8]Yaghouibi AR., Ansarin K., Hashemxadeh S et al
Takotsubo cardiomyopathy induced by emotional stress leading to severe mitral regurgitation
Int J Cardiol 2009;135:e85-e86
No review of intensity of blood pressure lowering treatment in Type 2 diabetes can ever be complete without taking into account four parameters, namely:-
(i)Hypertension as a risk factor for atrial fibrillation(AF)
(ii)The relationship between intensity of blood pressure lowering and mitigation of the risk of incident atrial fibrillation.
(iii)The association between diabetes and atrial fibrillation, including the possibility that this might be a causal relationship.
(iv) The association between obesity and atrial fibrillation, including the causal relationship between obesity and Type 2 diabetes.
Each of those parameters has a potential therapeutic dimension as follows:-
Hypertension is the most prevalent risk factor for atrial fibrillation[1], and it is now recognised that intensive lowering of blood pressure, down to a systolic blood pressure of < 120 mm Hg, generates a significant reduction in the risk of incident atrial fibrillation[2]. In the latter study 4003 subjects were randomly allocated to the strategy of achieving a goal systolic blood pressure of < 120 mm Hg, and 4019 were randomly allocated to achieve s goal systolic blood pressure of < 140 mm Hg. During a 5.2 year follow up intensive treatment was associated with 26% lower risk of incident AF(Hazard Ratio, 0.74;95% Confidence Interval 0.56-0.98)[2].
Given the association between diabetes and AF which was shown in the systematic review by Alija et al[3]...
No review of intensity of blood pressure lowering treatment in Type 2 diabetes can ever be complete without taking into account four parameters, namely:-
(i)Hypertension as a risk factor for atrial fibrillation(AF)
(ii)The relationship between intensity of blood pressure lowering and mitigation of the risk of incident atrial fibrillation.
(iii)The association between diabetes and atrial fibrillation, including the possibility that this might be a causal relationship.
(iv) The association between obesity and atrial fibrillation, including the causal relationship between obesity and Type 2 diabetes.
Each of those parameters has a potential therapeutic dimension as follows:-
Hypertension is the most prevalent risk factor for atrial fibrillation[1], and it is now recognised that intensive lowering of blood pressure, down to a systolic blood pressure of < 120 mm Hg, generates a significant reduction in the risk of incident atrial fibrillation[2]. In the latter study 4003 subjects were randomly allocated to the strategy of achieving a goal systolic blood pressure of < 120 mm Hg, and 4019 were randomly allocated to achieve s goal systolic blood pressure of < 140 mm Hg. During a 5.2 year follow up intensive treatment was associated with 26% lower risk of incident AF(Hazard Ratio, 0.74;95% Confidence Interval 0.56-0.98)[2].
Given the association between diabetes and AF which was shown in the systematic review by Alija et al[3], there is a potential for coexistence of diabetes to compound the risk of hypertension-related AF. In that systematic review longitudinal studies showed that, for patients with paroxysmal AF, diabetes was associated with 1.32 times increased likelihood of progression to non-paroxysmal AF(5 studies, pooled Odds Ratio, 1.32(95% CI, 1.07 - 1.62)[3].
Obesity is a risk factor, not only for hypertension and for Type 2 diabetes, but, also, for AF. In a review of the relationship between obesity and AF Javed at al cited a meta-analysis of 51 studies which generated a calculation showing that, for every 5-point increase in Body Mass Index there was an additional 20%-30% increase in incident AF.. Obesity-related AF, in turn is believed to be attributable to the pro-inflammatory state generated by obesity[4].
Therapeutic implications:-
Adjunctive use of agents with anti hypertensive properties, antidiabetic properties, as well as anti-inflammatory properties might be the ideal strategy for management of diabetes-related hypertension. This was shown to good effect in the use of dapagliflozin versus placebo as add-on treatment to angiotension converting enzyme inhibitor therapy(or angiotension receptor blocker treatment) and a diuretic[5]. In that study mean seated systolic blood pressure was reduced by 11.9 mm Hg(95% CI -13.7 to -9.82) in the dapagliflozin subgroup compared to the use of placebo (-7.62 mm Hg; 95% CI -9.72 to -5.51)[5]. Arguably, in that role, the anti-inflammatory activity of the SGLT-2 inhibitor[6], might confer the additional benefit of mitigating the risk of hypertension-related AF.
Alternatively, the obese diabetic patient who is also hypertensive might derive benefit from both the weight reduction associated with the use of glucagon-like peptide-1 receptor agonists(GLP receptor agonists) and the antihypertensive action of those agents[7].
A powerful case can also be made for optimising cardioprotection through the combined use of SGLT2-inhibitor therapy and GLP agonist therapy[8].
I have no conflict of interest.
References
[1]Middlesdorp ME., Ariyaratnam JP., Kamsani SH., Albert CM., Sanders P
Hypertension and atrial fibrillation
Journal of Hypertension 2022;40:2337-2352
[2]Soliman EZ., Rahman AKMF., Zhang Z-m et al
Effect of intensive blood pressure lowering on the risk of atrial fibrillation
Hypertension 2020;75:1391-1496
[3] Alija F., Buttia C., Reichlin T et al
Association of diabetes with atrial fibrillation types: a systematic review and meta analysis
Cardiovascular Diabetology 2021;20:230 oi.org/10.1186/s12933-021-01423-2
[4]Javed S., Gupta D., Lip GYH
Obesity and atrial fibrillation making inroads through fat
European Heart Journal: Cardiovascular Pharmacotherapy 20121;7:59-67
[5[Weber MA., Mansfield TA., Cain VA et al
Blood pressure and glycaemic effects of dapagliflozin versus placebo in patients with type 2 diabetes on combination antihypertensive therapy: a randomised double blind placebo controlled phase-3 study
Lancet Diabetes Endocrinology 2016;4:211-220
[6] Bendotti G., Montefusco L., Pastore I et al
The anti-inflammatory and immunological properties of SGLT2-inhibitors
Journal of Endocrinological Investigation 2023;46:2445-2452
[7]Ribeiro-Silva JC., Tavaras CAM., Girardi ACC
The blood pressure lowering effects of glucagon-like peptide-1-receptor agonists: A mini review of the potential mechanisms
Current Opinion in Pharmacology 2023;69:102355
[8[] Gourdy P., Darmon P., Dievart F., Halim J-M., Guerci B
Combining glucagon-like peptide-1 receptor agonists (GLP-1 Ras) and sodium glucose cotransporter-2 inhibitors(SGLT2is) in patients with type 2 diabetes mellitus(T2DM)
Cardiovascular Diabetology 2023;22:79 doi.org/10.1186/s12933-023-01798-4
The observation that older age is associated with fewer recurrences of pericarditis but more severe complications[1] needs to be qualified to include a recognition of the entity of acute pericarditis attributable to infective endocarditis(IE)[2],[3]..
A prospective cohort study which covered the period January 1990 to December 2007 enrolled 459 subjects with native valve infective endocarditis associated with 479 episodes of IE. Among those there was a subgroup of 118 subjects with pericardial effusion. In that cohort IE patients who did not have pericardial effusion had a mean age of 57 versus a mean age of 47.6 in those with pericardial effusion(p < 0.001 on multivariate analysis[2]. Large-to-very large pericardial effusions were associated with an increase in 1-year mortality(Odds Ratio 3.0; 95% Confidence Interval 1.2 to 7.9)[2].
An observational study enrolled 338 subjects embracing a wider spectrum of IE which included native valve infective endocarditis, prosthetic valve IE, and IE attributable to implantable electronic devices. In that study it was also shown that IE patients who had pericardial effusion were significantly(p < 0.003) younger than counterparts who did not have pericardial effusion[3].
neither of the two studies documented the presence of IE without cardiac murmurs.
Given the observation that IE patients with pericardial effusion have more severe infections than patients without pericardial effusions[2],[3], and...
The observation that older age is associated with fewer recurrences of pericarditis but more severe complications[1] needs to be qualified to include a recognition of the entity of acute pericarditis attributable to infective endocarditis(IE)[2],[3]..
A prospective cohort study which covered the period January 1990 to December 2007 enrolled 459 subjects with native valve infective endocarditis associated with 479 episodes of IE. Among those there was a subgroup of 118 subjects with pericardial effusion. In that cohort IE patients who did not have pericardial effusion had a mean age of 57 versus a mean age of 47.6 in those with pericardial effusion(p < 0.001 on multivariate analysis[2]. Large-to-very large pericardial effusions were associated with an increase in 1-year mortality(Odds Ratio 3.0; 95% Confidence Interval 1.2 to 7.9)[2].
An observational study enrolled 338 subjects embracing a wider spectrum of IE which included native valve infective endocarditis, prosthetic valve IE, and IE attributable to implantable electronic devices. In that study it was also shown that IE patients who had pericardial effusion were significantly(p < 0.003) younger than counterparts who did not have pericardial effusion[3].
neither of the two studies documented the presence of IE without cardiac murmurs.
Given the observation that IE patients with pericardial effusion have more severe infections than patients without pericardial effusions[2],[3], and also have worse prognosis[2],[3], there is an imperative to maintain a high index of suspicion for IE even when a patient with pericardial effusion presents without a murmur.
Two cases reinforce this imperative:-
A 28 year old woman, known to have a history of illicit use of intravenous drugs, presented with a history of dyspnoea and cough with purulent sputum. No cardiac murmurs were detected on clinical examination. nevertheless, focused cardiac ultrasound showed a small pericardial effusion an a tricuspid valve vegetation. Computed tomography pulmonary angiography showed multiple bilateral pulmonary nodules with cavitation most likely attributable to septic embolism form the tricuspid valve vegetation[4]..
A 71 year old man presented with fever and chest pain aggravated by breathing. Clinical examination did not detect pericardial friction rub or any murmurs. He was initially empirically treated with various antibiotic drug combinations.. Fourteen days later he had a repeat echocardiogram, and this showed moderate pericardial effusion with incipient tamponade. Colcichine was coprescribed. A subsequent pericardiocentesis yielded a purulent pericardial effusion. On polymerase chain reaction analysis the culprit pathogen was shown to be Clostridium septicum. Thereafter he was prescribed high dose intravenous penicillin to which he responded favourably. On day 52 a repeat echocardiogram showed minimal pericardial effusion. He was then discharged home. Fifteen days later he was readmitted with a history of increasing breathlessness.. A transpesophageal echocardiogram showed new, haemodynamically significant aortic valve regurgitation necessitating urgent aortic valve replacement. At operation an abscess was found near the aortic root. He died shortly after the operation.
Comment
In the first case there was already a high index of suspicion for IE, given the history of illicit intravenous drug use. Acting on that suspicion, even in the absence of a murmur, the patient had timely echocardiography, which validated the diagnosis of IE. In the second patient a case could be made for earlier and more frequent use of transoesophageal echocardiography following pericardiocentesis, in spite of the absence of a murmur.
I have no conflict of interest.
Reference
[1]Collini V., Vignut LS., Angriman F et al
Age-stratified patterns in clinical presentation, treatment, and outcomes in acute pericarditis ; a retrospective cohort study
Heart 2024;110;1139-1144
[2]Regueiro A., Falces C., Cervera C et al
Risk factors for pericardial effusion in native valve infective endocarditis and the influence on outcome
Am J Cardiol 2013;112:1646-1651
[3]Youssef GS., Mashaal MS., El-Remisy DR., Sorour KA., Rizk HH
Pericardial effusion in prosthetic and native valve infective endocarditis
Indian Heart Journal 2019;71:80-84
[4]Bacci M., oatel K., Carbrera G., Kalidova EI
Bedside echocardiography diagnosis of tricuspid valve infective endocarditis in the emergency department
CUREUS 2022;14:e29541
[5]Sulc D., Vanerkova M., Radvan M et al
Acute purulent pericarditis caused by Clostridium septicum
Cor et Vasa 2018;60:e407-e411
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.
Intriguingly, in the recent study, severe mitral regurgitation was present in as many as 10.3% of patients who did not have left ventricular outflow tract obstruction(LVOTO)[1]. This observation raises the question of whether or not mitral regurgitation(MR) might, in some of those cases, have been attributable to Takotsubo-related tethering of the mitral valve leaflets[2]. The latter was the underlying cause of severe MR in a 57 year old woman with previous history of treated hypertension who presented with chest pain and a blood pressure of 119/84 mm Hg. What we do not know is whether or not that blood pressure was her usual "on treatment" blood pressure or whether it represented a significant fall from her usual blood pressure. Her electocardiogram(ECG) showed ST segment elevation in leads V5 and V6. Coronary angiography did not show any obstructive lesion. Instead, she had stigmata of TTC, namely, apical left ventricular apical hypokinesis and basal hyperkinesis. Furthermore, she had eccentric mitral regurgitation associated with tethering of the anterior mitral leaflet. Neither LVOTO nor systolic anterior motion(SAM) of the mitral valve was observed. Her left ventricular ejection fraction(LVEF) amounted to 59.7%. After an uneventful clinical course she had a follow up which showed complete resolution of MR[2]. Leaflet tethering is believed also to be implicated in the aetiopathogenesis of TTC-related tricuspid regurgitation(TR)[3]. On occasions...
Show MoreNo review of intensity of blood pressure lowering treatment in Type 2 diabetes can ever be complete without taking into account four parameters, namely:-
Show More(i)Hypertension as a risk factor for atrial fibrillation(AF)
(ii)The relationship between intensity of blood pressure lowering and mitigation of the risk of incident atrial fibrillation.
(iii)The association between diabetes and atrial fibrillation, including the possibility that this might be a causal relationship.
(iv) The association between obesity and atrial fibrillation, including the causal relationship between obesity and Type 2 diabetes.
Each of those parameters has a potential therapeutic dimension as follows:-
Hypertension is the most prevalent risk factor for atrial fibrillation[1], and it is now recognised that intensive lowering of blood pressure, down to a systolic blood pressure of < 120 mm Hg, generates a significant reduction in the risk of incident atrial fibrillation[2]. In the latter study 4003 subjects were randomly allocated to the strategy of achieving a goal systolic blood pressure of < 120 mm Hg, and 4019 were randomly allocated to achieve s goal systolic blood pressure of < 140 mm Hg. During a 5.2 year follow up intensive treatment was associated with 26% lower risk of incident AF(Hazard Ratio, 0.74;95% Confidence Interval 0.56-0.98)[2].
Given the association between diabetes and AF which was shown in the systematic review by Alija et al[3]...
The observation that older age is associated with fewer recurrences of pericarditis but more severe complications[1] needs to be qualified to include a recognition of the entity of acute pericarditis attributable to infective endocarditis(IE)[2],[3]..
Show MoreA prospective cohort study which covered the period January 1990 to December 2007 enrolled 459 subjects with native valve infective endocarditis associated with 479 episodes of IE. Among those there was a subgroup of 118 subjects with pericardial effusion. In that cohort IE patients who did not have pericardial effusion had a mean age of 57 versus a mean age of 47.6 in those with pericardial effusion(p < 0.001 on multivariate analysis[2]. Large-to-very large pericardial effusions were associated with an increase in 1-year mortality(Odds Ratio 3.0; 95% Confidence Interval 1.2 to 7.9)[2].
An observational study enrolled 338 subjects embracing a wider spectrum of IE which included native valve infective endocarditis, prosthetic valve IE, and IE attributable to implantable electronic devices. In that study it was also shown that IE patients who had pericardial effusion were significantly(p < 0.003) younger than counterparts who did not have pericardial effusion[3].
neither of the two studies documented the presence of IE without cardiac murmurs.
Given the observation that IE patients with pericardial effusion have more severe infections than patients without pericardial effusions[2],[3], and...
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.
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