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)...

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.

The relationship between takotsubo syndrome, left ventricular hypertrabeculation/noncompaction, neurologic and neuromuscular disorders.

Takotsubo syndrome (TTS) and left ventricular hypertrabeculation/noncompaction (LVHT) have in common that they are only diagnosed since 1990. Diagnostic criteria and prognosis of affected patients are still debated and the knowledge about etiology and pathogenesis of both disorders is limited. Both abnormalities are associated with neurologic and neuromuscular disorders (NMD). We summarize the data about the relationship between TTS, LVHT and NMD. We identified 8 case reports about the co-incidence of TTS and LVHT (6 females, 2 males, age 0-76 years). In 2/8 cases recurrent TTS occurred after 8 and 10 months. In most of the patients, LVHT was diagnosed together with TTS, thus, it cannot be assessed if LVHT was present since birth or developed during life-time. In one case, LVHT was absent in a previous echocardiogram, developed de novo during TTS, and disappeared after 3 months. In 4/8 patients follow-up were reported, and in all of them, regression or disappearance of LVHT was observed. NMD or psychiatric disorders were reported in 7/8 patients. We conclude -limited by the small number of cases-that patients with LVHT and TTS seem to be frequently associated with NMD and have a high risk of recurrence. LVHT seems to disappear after TTS, but it remains unclear whether trabeculations in fact regress or are still present, but not more visible because of a decrease in left ventricular size resulting in smaller spaces between the trabeculations. Patients with LVHT and TTS require long-term follow-up to assess any changes of these abnormalities over time.

Subcutaneous implanted cardioverter-defibrillator in ventricular noncompaction, coronary artery disease and stroke.

Left ventricular hypertrabeculation/noncompaction (LVHT) is associated with arrhythmias. Guidelines for prevention of sudden cardiac death by implanted cardioverter-defibrillator (ICD) also apply to LVHT-patients. Right ventricular perforation by the ICD-lead is a matter of concern. Subcutaneous ICD (S-ICD) may overcome disadvantages of transvenous ICD in patients without a need for pacing therapy. We report a LVHT-patient with arterial hypertension, hyperlipidemia, coronary artery disease with an anterior-wall myocardial infarction 2004 and stroke without neurological deficits in 2018. Since ejection fraction of 33% remained unchanged despite bisoprolol, sacubitril/valsartan and spironolactone, he was treated with S-ICD for primary prevention of sudden cardiac death.

Left Ventricular Thrombi and Embolic Events in Takotsubo Syndrome despite Therapeutic Anticoagulation.

INTRODUCTION: Takotsubo syndrome (TTS) may be complicated by left-ventricular (LV) thrombus formation in 1.3-5.3% of patients. Risk factors for thrombi comprise apical TTS, elevated levels of C-reactive protein and troponine, thrombocytosis, persisting ST segment elevation and right-ventricular involvement. Embolic risk appears high, and anticoagulation is recommended. CASE PRESENTATION: We present 3 females, aged 60-82 years, with TTS-associated LV thrombi and cerebral embolism despite therapeutic anticoagulation. Two patients showed apical and 1 patient midventricular ballooning. In 2 patients LV thrombi had not been present at the first echocardiographic examination. LV thrombi were multiple and highly mobile in 2 patients; 1 patient had a single immobile thrombus associated with spontaneous echocardiographic contrast (SEC). In each case, 3 of the described risk factors for LV thrombus formation were identified. The embolic stroke occurred 41-120 h after TTS symptom onset and 21-93 h after the initiation of therapeutic anticoagulation. Two patients were discharged with a neurological deficit, and 1 of them eventually died as a consequence of the stroke. LV thrombectomy to prevent embolism, which has been reported in a small number of cases, had not been considered in our patients. CONCLUSION: At present, the management of patients with TTS-related thrombi is still unclear, and further studies are urgently needed to assess the best methods for imaging and anticoagulation and to determine the role of thrombolysis and cardiac surgery. Until these studies are available, we suggest the following approach: patients with a TTS-related thrombus should be monitored by echocardiography while receiving anticoagulation. In case of highly mobile LV thrombi, the heart team may consider cardiac surgery to prevent systemic embolism. The role of SEC in TTS remains to be determined.

Left Ventricular Noncompaction Syndrome: Genetic Insights and Therapeutic Perspectives.

PURPOSE OF REVIEW: To discuss the association of left ventricular hypertrabeculation/noncompaction (LVHT/LVNC/NCCM) with genetic disease and to outline the therapeutic options for non-symptomatic and symptomatic LVHT. RECENT FINDINGS: A number of new mutated genes have been recently detected being associated with LVHT. There are indications that microtubules changing cell polarity, the transcription factor Nkx2-5, and NOTCH-1 signaling are involved in the pathogenesis of LVHT. There are also indications that the PKC signaling pathway, which is involved in the regulation of gap junction intercellular communication, is disturbed in LVHT. LVHT is the same as LVNC and is associated with pathogenic variants in > 110 mtDNA or nDNA genes. LVHT has been also reported in > 15 chromosomal defects. However, a causal relation between any of these variants and LVHT has not been proven. There is no general agreement on the treatment of LVHT. According to expert opinions, LVHT patients require anticoagulation if they meet the criteria for anticoagulation or an ICD if they meet the appropriate criteria. Heart failure therapy is equal to patients with other causes of heart failure.

Severe Acquired Hypokalemic Paralysis in a Bodybuilder After Self-Medication With Triamterene/Hydrochlorothiazide.

BACKGROUND: Severe hypokalemia with severe neurological impairment and electrocardiogram (ECG) abnormalities due to the misuse of triamterene/hydrochlorothiazide (HCTZ) in a bodybuilder has not yet been reported. CASE REPORT: A 22-year-old bodybuilder developed acute generalized muscle cramps, sensory disturbance of the distal lower and upper limbs, quadriparesis, and urinary retention. These abnormalities were attributed to severe hypokalemia of 1.8 mmol/L (normal range 3.4-4.5 mmol/L) due to misuse of triamterene/HCTZ together with fluid restriction. He was cardiologically asymptomatic, but ECG revealed a corrected QT (QTc) interval of 625 ms. On intravenous application of fluids along with intravenous and oral substitution of potassium, his condition rapidly improved, such that the sensory disturbances, quadriparesis, and bladder dysfunction completely resolved within 2 days after admission. CONCLUSIONS: Self-medication with diuretics along with fluid restriction may result in severe hypokalemia, paralysis, and ECG abnormalities. Those responsible for the management of bodybuilding studios and competitions must be aware of the potential severe health threats caused by self-medication with diuretics and anabolic steroids. Although triamterene is potassium-sparing, it may enhance the potassium-lowering effect of HCTZ.

Side effects of whole-body electro-myo-stimulation.

Whole-body-electro-myo-stimulation (WB-EMS) has been introduced as an alternative to physical training. The aim of the review is to summarize the data about indications and side effects of WB-EMS.A literature search in PubMed disclosed 11 randomized trials, 3 cohort studies, and 7 case reports. From healthy volunteers, enormous creatine kinase (CK) elevations were reported. There is a lack of data about biological consequences of WB-EMS on other organs. In randomized trials, CK levels were not investigated, but several patients discontinued WB-EMS because of "muscular discomfort." Contraindications for WB-EMS are not clearly defined. Nine cases of rhabdomyolysis after WB-EMS were found, preferentially after the first application.Regulatory authorities should increase the safety of WB-EMS. Patients with a history of rhabdomyolysis should not undergo WB-EMS and those experiencing rhabdomyolysis should be neurologically investigated. Since the value of WB-EMS as an alternative to physical exercise is uncertain, we need to proof or disproof its benefit.

Respiratory insufficiency from myasthenia gravis and polymyositis due to malignant thymoma triggering Takotsubo syndrome.

BACKGROUND: Takotsubo syndrome (TTS) is a non-ischaemic cardiomyopathy with sudden but transient systolic dysfunction. TTS mimics myocardial infarction clinically, chemically, and electrocardiographically but echocardiography typically shows apical ballooning and coronary angiography is normal. TTS has not been reported in a patient with myasthenia gravis (MG) and polymyositis due to a malignant thymoma. CASE REPORT: Two weeks prior to admission, a 76-year-old female developed dysarthria, chronic coughing and disabling myalgias of the entire musculature. Since there was hyper-CKemia and elevated troponin, myocardial infarction was suspected. During swallowing of the antithrombotic medication on admission, she experienced apnoea, requiring cardio-pulmonary resuscitation with intubation and mechanical ventilation. Further diagnostic work-up precluded coronary heart disease but revealed TTS. Upon neurologic work-up, MG and polymyositis were diagnosed but the response to cholinergic drugs and plasmapheresis was poor. TTS was attributed to stress and anxiety from MG-associated respiratory insufficiency. The further course was complicated by recurrent supraventricular bradyarrhythmias and respiratory insufficiency. Upon thoracic CT a thymoma was suspected. Two months after admission, the mediastinal tumour was resected and malignant thymoma WHO BII infiltrating the mediastinum (modified Masaoka-Koga II/2) was diagnosed. CONCLUSIONS: This case shows that TTS may be triggered by stress from respiratory insufficiency during a myasthenic crisis, MG may be associated with polymyositis, cholinergic medication may trigger bradyarrhythmias, and cholinergic drugs and plasmapheresis may exhibit a poor effect if malignant thymoma and polymyositis are present.

Tako-tsubo cardiomyopathy with transient global amnesia and cerebellar embolic stroke triggered by existential fear.

BACKGROUND: Embolic stroke is a complication of Tako-Tsubo-cardiomyopathy (TTC), transient left ventricular dysfunction mimicking myocardial infarction without coronary culprit lesion explaining the whole left ventricular dysfunction. Transient global amnesia (TGA) is characterized by sudden onset of anterograde amnesia without compromise of other neurologic functions. CASE REPORT: A 57 years old female was admitted because of sudden confusion and loss of her memory after emotional stress. TGA was diagnosed. Because of chest pain and laboratory tests indicating myocardial ischemia, she underwent coronary angiography which was normal. Within the following 24h her memory improved. She complained about severe vertigo and cerebral magnetic resonance imaging showed a recent ischemia in the left cerebellum. CONCLUSIONS: TGA is not a disease for the neurologists exclusively but also cardiac comorbidities have to be considered and cardiologists should be involved in the acute care of these patients in order not to overlook life-threatening diseases.

Recurrent venous thrombosis under rivaroxaban and carbamazepine for symptomatic epilepsy.

BACKGROUND: The direct oral anticoagulant (DOAC) rivaroxaban, an oral Factor Xa inhibitor, is increasingly used as an alternative to vitamin-K-antagonists (VKAs). Absorption and elimination of DOACs are dependent on the permeability glycoprotein (P-gp) efflux transporter protein system, and DOACs are substrates of the hepatic cytochrome P 450 3A4 (CYP3A4) enzymes. Therefore, drug-interactions may occur when DOACs are administered with drugs affecting the activity of P-gp or CYP3A4 systems. Several antiepileptic drugs like carbamazepine are known to affect P-gp and CYP3A4-activity. CASE REPORT: A 55-year-old male was admitted because of pain and swelling of his right leg spontaneously since 2 days. He was under a therapy with 20mg rivaroxaban since 4 months because of an unprovoked venous thrombosis of his right leg. He had a history of poliomyelitis at age 6 months, structural epilepsy due to poly-microgyria with complex partial seizures with secondary generalization since age 6 years, why he was treated with carbamazepine (900mg/d). He reported to be highly adherent to his anticoagulant and antiepileptic medication. Anti-Xa activity was <20ng/ml according to a rivaroxaban calibrated anti-factor Xa assay. Therapy with rivaroxaban was stopped, and low-molecular-weight heparin, followed by phenprocoumon, was started. CONCLUSION: The combination of DOACs with carbamazepine, an inducer of P-gp and CYP3A4-activity, should be avoided since the anticoagulant effect is decreased. There is an urgent need to increase our knowledge and physicians' awareness about the potential of drug-drug interactions of DOACs.

Atrial fibrillation and stroke as initial manifestations of painless type A aortic dissection.

Aortic dissection is diagnostically challenging, especially in pain-free patients. Detection of acute ischemic stroke secondary to painless aortic dissection is a challenge for emergency physicians and neurologists. We report a previously healthy 58-years old female, admitted because of nausea, dizziness, somnolence, a left-sided hemiparesis and arterial hypotension. The electrocardiogram showed atrial fibrillation with ST-elevations and ST-depressions. Perfusion CT-imaging showed a dilatation of the aortic arch and intraluminal structures indicating an intima flap of aortic dissection. Four hours after onset of symptoms the patient died on the way to the cardiac surgery. In conclusion, apart from imaging the aortic arch by computed tomography in acute stroke patients, the electrocardiogram may be indicative for aortic dissection if it shows signs for myocardial ischemia in previously healthy patients.

Age-dependency of prescribing patterns of oral anticoagulant drugs in Austria during 2011-2014.

Direct oral anticoagulants (DOACs) have been introduced within the last years as alternative to vitamin K antagonists (VKAs) as oral anticoagulant drugs (OAC). The mean/median age of the patients included in DOAC-investigating trials was 70-72 years. The age-pattern of patients to whom DOAC are prescribed in clinical settings is largely unknown. Thus, aim of the study was to assess the age-pattern of patients who received OAC in the years 2011-2014 in Austria. The data analysis refers to the accounting data of the 13 major health insurance funds, covering >97 % of the Austrian population. The number of patients who received OAC in 2011-2014 increased by 43 % (182,464-261,347). Patients who received DOACs increased nearly fivefold (20,927-96,247), whereas patients who received VKAs increased by only 2 % (161,537-165,100). In 2011, the age of patients receiving VKAs was higher than DOACs (72 vs. 68 years), whereas in 2014, the age of the patients receiving VKAs was lower than DOACs (73 vs. 74 years). The proportion of patients ≥80 years receiving VKAs declined from 26 to 21 % of all OAC, receiving DOACs increased from 1 to 12 %. Among nonagenarians, the proportion of patients receiving VKAs remained 2 % (3316-5858), whereas the proportion of patients receiving DOACs increased 40-fold (91-4296). DOACs are prescribed to patients ≥80 years, although there are is a lack of data about efficacy and safety. There is an urgent need for data about this patient group. Since a randomized trial is rather unlikely in this specific age group we suggest subgroup analyses about octo-and nonagenarians, in case they have been included in previously completed or still ongoing trials or registries for OAC.

Postnatal Outcome of Fetal Left Ventricular Hypertrabeculation/Noncompaction.

Left ventricular hypertrabeculation/noncompaction (LVHT) is a cardiac abnormality of unknown etiology. Prenatal diagnosis of LVHT can be established by fetal echocardiography. A review of 106 published cases showed that 46 cases with prenatally diagnosed LVHT were alive 0.5-120 months after birth. Since the course of cases with prenatally LVHT after publication is unknown, we aimed to collect follow-up-information. Information regarding vital status, cardiac and extracardiac morbidity was gathered by contacting the authors of the 46 cases. Fourteen of the 28 authors answered and gave information about 18 cases (six females, seven males, five gender-unknown, age 18 months to 10 years, mean follow-up 60 months). No differences were found between the 18 cases with follow-up and the 28 cases without follow-up regarding age, gender, cardiac or extracardiac comorbidities, and interventions. Three of the 18 cases had died subsequently from heart failure, osteosarcoma, and enterocolitis, respectively. Mutations or chromosomal abnormalities were found in six of the seven examined patients, extracardiac abnormalities in nine patients. Three patients received a pacemaker because of complete AV block, and two patients underwent heart transplantation. Cardiac surgical or interventional procedures were carried out in four patients. None suffered from malignant arrhythmias or had a cardioverter-defibrillator implanted. Based on the limited information, there are indications that cases with fetal diagnosis of LVHT have a continuing morbidity and mortality, even if they receive appropriate care. Since fetal LVHT is frequently associated with genetic abnormalities, further research about survival and underlying genetic causes is needed.