Atrio-oesophageal fistula after radiofrequency ablation of atrial fibrillation misinterpreted as COVID-19 infection.

Awareness of the various clinical manifestations and diagnostic pitfalls in patients with atrio-oesophageal fistula is necessary among healthcare professionals.

Comments on "Tako-Tsubo syndrome in patients with COVID-19: a single centre retrospective case series".

Dear Editor, We read with interest the article by Alonzo et al. about a retrospective study of four patients with Takotsubo syndrome (TTS), which was attributed to SARS-CoV-2 infection (SC2I)...

Adverse events and drug-drug interactions of sodium glucose co-transporter 2 inhibitors in patients treated for heart failure.

INTRODUCTION: Sodium glucose co-transporter 2-inhibitors (SGLT2-I), antihyperglycemic agents, are increasingly prescribed in chronic heart failure (CHF). Their risk for drug-drug interactions (DDI) seems low. Safety-data derive mainly from diabetes-patients. This review aims to summarize adverse-events (AE) and DDI of the SGLT2-I dapagliflozin, empagliflozin and sotagliflozin in patients with CHF. AREAS COVERED: Literature-search-terms in PubMed were 'adverse event/drug-drug interaction' and 'heart failure AND 'dapagliflozin' OR 'empagliflozin' OR 'sotagliflozin.'AEreported in randomized controlled trials (RCT) comprisegenitaland urinary-tract infections, hypotension, ketoacidosis, renal impairment, hypoglycemia, limb-amputations, Fournier's gangrene, bone-fractures, hepatopathy, pancreatitis, diarrhea, malignancy and venous thromboembolism. Their incidence is largely unknown, since they were not consistently evaluated in RCT of CHF. Further AE from meta-analyses, pharmacovigilance reports, case-series and case-reports include erythrocytosis, hypertriglyceridemia, myopathy, sarcopenia, skin problems, ventricular tachycardia, and urinary retention. The maximal observation period of RCT in CHF was 26 months.DDI were mainly studied in healthy volunteers for 3-8 days. In CHF or diabetes-patients, DDI were reported with interleukin-17-inhibitors, linezolid, lithium, tacrolimus, valproate, angiotensin-receptor-neprilysin-inhibitors and intravenous iron. EXPERT OPINION: Guidelines recommend treatment with SGLT2-I for CHF but no data on AE during long-term therapy and only little information on DDI are available, which stresses the need for further research. Evidence-based recommendations for ketoacidosis-prevention are desirable.

Cannabidiol's impact on drug-metabolization.

IMPORTANCE: Products containing cannabidiol(CBD) are easily accessible. CBD is reported to inhibit the drug-metabolizing proteins(DMP) Cytochrome P450(CYP)3A4/5, CYP2C9, CYP2B6, CYP2D6, CYP2E1, CYP1A2, CYP2C19, carboxylesterase 1(CES1), uridine 5'diphospho-glucoronosyltransferase(UGT)1A9, UGT2B7, P-glycoprotein(P-gp) and Breast Cancer Resistance Protein(BCRP). The relevance of CBD-drug interactions is largely unknown. Aim of the study was to identify drugs, potentially interacting with orally ingested CBD, to assess whether CBD-drug interactions have been reported, and if substrates of DMP are frequently prescribed drugs. OBSERVATIONS: Identified were 403 drugs as substrates of DMP. CBD-drug interactions were reported for 53/403 substrates in humans (n = 25), in vivo (n = 13) or in vitro (n = 15). In 31/53 substrates, CBD induced an increase, in 1/53 a decrease, in 4/53 no change in the substrate level. For 5/53 substrates, the results were controversial, and in 12/53 no substrate levels were reported. Among the 30 most frequently prescribed drugs in Germany were 67% substrates of DMP and among the 50 most frequently prescribed drugs in the USA 68%. RELEVANCE AND CONCLUSIONS: There is an urgent need for pharmacologic studies on CBD-drug interactions. Patients should be educated on the potential risk and awareness should be increased among physicians. Regulatory authorities should become aware of the problem and start an initiative on an international level to increase the safety of CBD.

Necrotizing pancreatitis, microangiopathic hemolytic anemia and thrombocytopenia following the second dose of Pfizer/BioNTech COVID-19 mRNA vaccine.

Implementing vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major asset in slowing down the coronavirus disease 2019 (COVID-19) pandemic. For mRNA vaccines, the main severe adverse events reported in pharmacovigilance systems and post-authorization studies were anaphylaxis and myocarditis. Pancreatitis after Pfizer/BioNTech COVID-19 vaccination has been reported only in 10 patients.We report a 31-year-old female with a history of borderline personality disorder, intravenous drug abuse, allergic asthma, eating disorder, psoriatic arthritis treated with tofacitinib, neurogenic bladder disturbance, cholecystectomy, recurrent thoracic herpes zoster, vaginal candida infections and urinary tract infections, who developed pancreatitis associated with thrombotic microangiopathy and hemolytic-uremic syndrome 10 days after the second vaccination, whereas the first has been well tolerated. She was treated by plasma exchange, and eventually by transgastric drainage with implantation of a plastic stent to remove fluid abdominal retentions. She was discharged after 19 days. Since then her condition has improved continuously. Computed tomography after 12 months did not reveal retentions anymore.As other causes of pancreatitis have been excluded, this case of acute pancreatitis, microangiopathic hemolytic anemia and thrombocytopenia, temporally associated with the Pfizer-BioNTech COVID-19 vaccine, suggests a causal link.

Stroke prevention in an octogenarian with atrial fibrillation, cerebral amyloid angiopathy and intracerebral hemorrhage.

Left-atrial-appendage-closure (LAAC) is suggested as alternative to antiplatelet/anticoagulant therapy (AP/AC) for stroke-prevention in patients with cerebral-amyloid-angiopathy (CAA), intracerebral hemorrhage (ICH) and atrial fibrillation (AF). Disadvantages of LAAC are the need for postinterventional AP and impairment of left atrial function, thus promoting heart-failure. Therefore, in an 83-year-old edoxaban-treated AF-patient with ICH and CAA, only antihypertensive therapy with neither AP/AC nor LAAC was recommended. Twenty-seven months without stroke/ICH support this strategy, which needs confirmation by a randomized-trial.

Drug-drug interactions with direct oral anticoagulants for the prevention of ischemic stroke and embolism in atrial fibrillation: a narrative review of adverse events.

INTRODUCTION: In randomized trials, direct oral anticoagulants (DOAC) were non-inferior to the vitamin-K-antagonist (VKA) warfarin in preventing stroke/embolism in patients with atrial fibrillation (AF). DOAC are substrates for P-glycoprotein (P-gp), CYP3A4 and CYP2C9. The activity of these enzymes is modulated by several drugs which might induce pharmacokinetic drug-drug interactions (DDI). Drugs affecting platelet function have the potential for pharmacodynamic DDI of DOAC. AREAS COVERED: The literature was searched for: 'dabigatran,' 'rivaroxaban,' 'edoxaban,' or 'apixaban' and drugs affecting platelet function, CYP3A4-, CYP2C9- or P-gp-activity. Reports about bleeding and embolic events attributed to DDI with DOAC in AF-patients were found for 43 of 171 drugs with interacting potential (25%), most frequently with antiplatelet and nonsteroidal anti-inflammatory drugs. Whereas a co-medication of platelet-affecting drugs is invariably reported to increase the bleeding risk, the findings regarding P-gp-, CYP3A4- and CYP2C9- activity-affecting drugs are ambiguous. EXPERT OPINION: Tests for plasma DOAC-levels and information about DDI of DOAC should be widely available and user-friendly. If advantages and disadvantages of DOAC and VKA can be investigated exhaustively, individualized anticoagulant therapy can be offered to patients, considering co-medication, comorbidities, genetic and geographic factors and the health care system.

Surgical Transmitral Thrombectomy to Prevent Recurrent Stroke in Acute Myocardial Infarction.

Left ventricular (LV)-thrombi occur in up to 14 % of patients with acute myocardial infarction (AMI) in the era of primary percutaneous coronary intervention. For these patients, anticoagulant therapy (AC) is recommended by AMI-guidelines. When, despite AC, LV-thrombi lead to embolism, surgical thrombectomy is an option, which is not mentioned or not recommended in AMI-guidelines. We report a 46-year old female patient with AMI. An 80 % stenosis of the proximal left anterior descending coronary artery was treated by a drug-eluting stent. Thrombi within the akinetic LV-apex became mobile despite AC and dual antiplatelet therapy, and a cerebellar stroke occurred. By a transmitral surgical approach with endoscopic assistance the thrombi were completely removed. Postoperative course and 12-months follow-up were uneventful. LV-thrombi should be observed carefully regarding changes in morphology. Surgical thrombectomy of LV-thrombi is a rare treatment option to prevent imminent embolism. Benefits versus risks of surgical removal of LV-thrombi need to be carefully weighted.

Before blaming the tooth extraction for the TTS, consider alternative triggers.

Takotsubo syndrome (TTS), also known as stress cardiomyopathy; is characterized by a clinical presentation similar to that of myocardial infarction but with normal coronary arteries. Four subtypes of TTS are distinguished, the classical type (apical form), the basal subtype, the reverse subtype, and the global subtype. TTS is triggered by physical stress in one-third of cases, by psychological stress in another third, and in the remaining third of cases the trigger remains unknown. Whether stress during tooth root extraction can trigger TTS is unknown but some rare reports suggest that such a dental procedure can trigger TTS. However, before tooth root extraction can be held responsible for triggering TTS, various different causes must be ruled out.

Aortic root replacement for aortic root aneurysm with severe aortic regurgitation and incidentally detected left ventricular hyper-trabeculation/noncompaction.

A 54-year-old male with severe aortic regurgitation (AR), aortic root aneurysm, left ventricular hyper-trabeculation/noncompaction (LVHT) and systolic dysfunction with a left ventricular ejection fraction (LVEF) of 52% underwent successful aortic root replacement. Intraoperative video-endoscopy confirmed LVHT. At 3-year follow-up, he remains in an excellent clinical condition and echocardiography shows an improvement of the systolic function, LVHT and LVEF of 66%. Timely surgical correction of severe AR may also lead to improvement of systolic function in a patient with LVHT.

Successful pregnancy in left ventricular hypertrabeculation/noncompaction with implanted cardioverter/defibrillator and a variant in the TPM1 Gen (c.425A > T) in mother and child.

Pregnancy in left ventricular hypertrabeculation/noncompaction (LVHT) is a matter of concern due to the risk for arrhythmia or heart failure (HF). This risk seems higher if arrhythmias have been already diagnosed before pregnancy. Pregnancies in LVHT cases with implanted cardioverter-defibrillators (ICD) are rarely reported.We report pregnancy of and delivery to a 28-year old patient with hypertrophic phenotype of LVHT with ICD, implanted 11 years previously for secondary prevention of sudden cardiac death, in whom genetic analysis disclosed a variant in the TPM1 Gen (c.425A > T). Until the 28th gestational week (GW), the pregnancy was without problems, then increasing HF due to diastolic dysfunction developed. In GW34, she was treated with atosiban for tocolysis because of premature labor. Due to aggravation of HF, preterm delivery by cesarean section in spinal anesthesia in GW35 was carried out. Delivery and maternal postpartal course were without problems, HF regressed. ICD interrogation did not show any arrhythmia.Pregnancy and delivery can be managed safely in hypertrophic phenotype of LVHT with ICD under interdisciplinary surveillance. Diastolic dysfunction may occur in the third trimester and lead to HF. Tocolytic drugs should be used with caution, even though the drugs are assumed to be safe regarding cardiovascular complications. Learning objective: Pregnancy and delivery can be managed safely in hypertrophic phenotype of left ventricular hypertrabeculation/noncompaction with implanted cardioverter-defibrillators under interdisciplinary surveillance. Diastolic dysfunction may occur in the third trimester and lead to heart failure. Tocolytic drugs should be used with caution, even though the drugs are assumed to be safe regarding cardiovascular complications.

Stroke and embolism in patients with left ventricular hypertrabeculation/noncompaction.

OBJECTIVES: Left ventricular hypertrabeculation/noncompaction(LVHT) is characterized by extensive trabeculations. LVHT has been reported to be associated with stroke or embolism(S/E). Aim of the study was to compare characteristics and prognosis of LVHT-patients with and without S/E to identify potential risk factors for S/E. MATERIALS AND METHODS: Retrospectively included were consecutive patients with echocardiographically diagnosed LVHT in a cardiologic department in 1995-2020. Baseline characteristics and follow-up data were collected. The etiology of S/E was assessed by applying the Trial of Org 10172 in Acute Stroke Treatment(TOAST) criteria. RESULTS: The follow-up of 319 patients, mean age 53 years, 30% females, was 7.4 ± 6 years. In 49 patients(15%), either stroke(n = 44), peripheric embolism(n = 3) or both(n = 2) occurred. The etiology of S/E was cardioembolic(n = 32), atherothrombotic(n = 12), undetermined(n = 4) and intracerebral hemorrhage(n = 1). S/E occurred in 31 patients before, in 15 patients after and in 3 patients before as well as after the diagnosis of LVHT. Patients with S/E were older, suffered more frequently from arterial hypertension, diabetes mellitus, atrial fibrillation, neuromuscular disorders and heart transplantation than patients without S/E. Of the patients with S/E, only 8% were without risk factors for S/E. For the patients in whom S/E occurred after the diagnosis of LVHT, the rate of S/E was 0.74%/year. The death rate was 4.17%/year in patients with and without S/E. CONCLUSION: Cardiovascular risk factors are more prevalent in LVHT-patients with than without S/E. S/E in LVHT-patients is not always cardioembolic why investigations for etiology are useful. LVHT by itself seems to be only a minor risk factor for S/E.

Usage of the wearable cardioverter-defibrillator during pregnancy.

Background: Pregnancy can trigger or aggravate the risk for life-threating arrhythmias in cardiac diseases. Pregnancy is associated with reluctance for implantable cardioverter-defibrillators (ICD) due to concerns about radiation. Thus, the wearable cardioverter-defibrillator (WCD) might be an option during pregnancy. Aim of the study was to collect experiences about the use of WCD in pregnancy. Methods and results: This study retrospectively included eight women who received a WCD during pregnancy. They suffered from ventricular tachycardia (VT) without known cardiac disease (n = 3), Brugada syndrome (n = 1), hypertrophic cardiomyopathy (n = 1), dilated cardiomyopathy (n = 1), non-compaction (n = 1), and survived sudden cardiac arrest during a preceding pregnancy (n = 1). WCD usage was started between 13 and 28 weeks of gestation. WCD wearing period ranged from 3 days to 30.9 weeks, WCD wearing time ranged from 13.0 to 23.7 h per day. Two women (25%) abandoned WCD already during pregnancy. Neither appropriate nor inappropriate WCD shocks were recorded. Antiarrhythmic management included beta-blockers (n = 5) and flecainide (n = 2). After delivery, ICD were implanted (n = 4), refused (n = 2) and estimated not necessary after successful catheter ablation (n = 2). Conclusion: Uneventful pregnancy is possible in women at risk for sudden cardiac death by interdisciplinary monitoring and diligent pharmacotherapy protected by the WCD. Since no WCD shocks were recorded, the effectiveness of WCD during pregnancy is still unclear. However, arrhythmia detection by WCD was very good despite the changed anatomy in pregnancy. Nevertheless, further studies are necessary to assess effectiveness of WCD in pregnant women. Furthermore, efforts should be made to increase the wearing adherence of WCD during pregnancy.

2022 HRS expert consensus statement on evaluation and management of arrhythmic risk in neuromuscular disorders.

This international multidisciplinary document is intended to guide electrophysiologists, cardiologists, other clinicians, and health care professionals in caring for patients with arrhythmic complications of neuromuscular disorders (NMDs). The document presents an overview of arrhythmias in NMDs followed by detailed sections on specific disorders: Duchenne muscular dystrophy, Becker muscular dystrophy, and limb-girdle muscular dystrophy type 2; myotonic dystrophy type 1 and type 2; Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy type 1B; facioscapulohumeral muscular dystrophy; and mitochondrial myopathies, including Friedreich ataxia and Kearns-Sayre syndrome, with an emphasis on managing arrhythmic cardiac manifestations. End-of-life management of arrhythmias in patients with NMDs is also covered. The document sections were drafted by the writing committee members according to their area of expertise. The recommendations represent the consensus opinion of the expert writing group, graded by class of recommendation and level of evidence utilizing defined criteria. The recommendations were made available for public comment; the document underwent review by the Heart Rhythm Society Scientific and Clinical Documents Committee and external review and endorsement by the partner and collaborating societies. Changes were incorporated based on these reviews. By using a breadth of accumulated available evidence, the document is designed to provide practical and actionable clinical information and recommendations for the diagnosis and management of arrhythmias and thus improve the care of patients with NMDs.