Left ventricular hypertrabeculation/noncompaction, cardiac phenotype, and neuromuscular disorders.

BACKGROUND: The prognosis of patients with left ventricular hypertrabeculation/noncompaction (LVHT) and its association with neuromuscular disorders (NMDs) is a controversial topic. The aim of this study was to assess whether the prognosis of LVHT patients is dependent on cardiac phenotype and the presence of NMDs. METHODS: Consecutive patients who were diagnosed with LVHT between 1995 and 2016 were included in the study. Cardiac phenotype was classified according to the recommendations of the European Society of Cardiology as: "dilated" if the left ventricular end-diastolic diameter (LVEDD) was >57 mm and left ventricular fractional shortening (FS) was ≤25%; "hypertrophic" if LVEDD was ≤57 mm, FS > 25%, and left ventricular posterior wall (LVPWT) and interventricular septal thickness (IVST) were both >13 mm; "intermediate" if LVEDD was >57 mm and FS > 25% or if LVEDD was ≤57 mm and FS ≤ 25%; and "normal" if LVEDD was ≤57 mm, FS > 25%, and IVST and LVPWT ≤ 13 mm. Therapy was carried out by the treating physicians. RESULTS: LVHT was diagnosed in 273 patients (80 females, 53 ± 16 years). The phenotype was assessed as dilated in 46%, hypertrophic in 8%, intermediate in 17%, and normal in 29% of the patients. Of these patients, 72% underwent neurological examinations, and an NMD was found in 76%. Over a period of 7.4 years (±5.7), 84 patients died and six underwent cardiac transplantation. The highest mortality rate was observed in the dilated and the lowest in the hypertrophic cardiac phenotype groups. Among the dilated phenotype, mortality was higher in patients with than without NMDs. CONCLUSION: Patients with LVHT and dilated cardiac phenotype have a worse prognosis than patients with a hypertrophic or intermediate/normal cardiac phenotype, especially if they suffer from NMDs.

Relevance of P-glycoprotein in stroke prevention with dabigatran, rivaroxaban, and apixaban.

BACKGROUND: The new oral anticoagulants (NOAC) dabigatran etexilate, rivaroxaban, and apixaban show similar efficacy for stroke prevention in patients with atrial fibrillation (AF) as the vitamin K antagonist warfarin. Absorption of NOACs is dependent on the intestinal P-glycoprotein (P-gp) system and P-gp activity is modulated by a variety of drugs and food components. OBJECTIVE: The aim of this review is to give an overview of P-gp-associated drug-drug and drug-food interactions with NOACs in AF patients. METHODS: A literature search was carried out by screening MEDLINE for the terms dabigatran, rivaroxaban, apixaban, P-glycoprotein, and atrial fibrillation from 1998 to 2013. Randomized clinical trials, longitudinal studies, case series, and case reports were included. RESULTS: Concomitant medication with proton pump inhibitors, amiodarone, clarithromycin, and verapamil increased bioavailability whereas rifampicin decreased the bioavailability of dabigatran. Coadministration of erythromycin, clarithromycin, fluconazole, ketoconazole, and ritonavir increased rivaroxaban plasma concentrations. No data were found on apixaban and P-gp-modulating drugs or on NOACs and food components modulating P-gp. The clinical relevance of interactions between NOACs and P-gp-modulating drugs or food components is largely unknown as bleeding complications under NOACs and P-gp-inhibiting drugs are mainly reported from patients with concomitant renal failure. CONCLUSION: There is an urgent need to investigate the role of P-gp-modulating substances as potential sources of drug-drug and drug-food interactions. A thorough analysis of the data accumulated in the three large NOAC trials regarding the role of P-gp-modulating drugs in bleeding and embolic events is desirable. Pharmacological studies should investigate the influence of P-gp-modulating drugs and food on NOAC plasma concentrations and coagulation parameters. When prescribing NOACs, patients should be informed about the potential interactions with drugs and herbal drugs. Patients who develop bleeding or embolic events under treatment with NOACs should be investigated for co-medications as well as for over-the-counter drugs and dietary habits. In post-marketing surveillance of NOACs, the association with drug or food intake with complications, bleeding, and embolic events should be registered.

Gastrointestinal bleeding under dabigatran.

Dabigatran-absorption is dependent on the intestinal P-glycoprotein (P-gp)-system, and P-gp activity is modulated by several drugs. We report an 83-old female with atrial fibrillation who developed gastrointestinal bleeding. She was under a therapy with non-steroidal anti-inflammatory drugs (NSAID) and P-gp-modulating drugs and renal function was impaired. We conclude that NSAID and P-gp-modulating drugs should be avoided in dabigatran-treated patients. If renal function deteriorates the dabigatran-dosage should be reduced or the therapy should be stopped. There is an urgent need to increase knowledge about drug interactions with dabigatran.

Beneficial effect of ivabradine in dilated cardiomyopathy from Becker muscular dystrophy.

OBJECTIVES: The I(f) blocker ivabradine reduces heart rate and improves systolic function without causing arterial hypotension. Ivabradine has not been reported to improve cardiac involvement in Becker muscular dystrophy (BMD). CASE REPORT: In a 22-year-old Vietnamese male with BMD, cardiac involvement became apparent at age 19 years with reduced systolic function, which was treated with ramipril. At the age of 20 years, he developed sinus tachycardia, leg edema, coughing, and arterial hypotension. Dilated cardiomyopathy was diagnosed and ramipril was successfully replaced by candesartan, ivabradine, and furosemide. An attempt to discontinue ivabradine and increase candesartan was followed by recurrence of sinus tachycardia and reduction of blood pressure. Under ivabradine, candesartan, and spironolactone, which replaced furosemide, he achieved heart rates between 60 and 80 beats/min and systolic blood pressure values between 85 and 105 mmHg without heart failure. CONCLUSION: Ivabradine normalizes sinus tachycardia and resolves heart failure in patients with dilated cardiomyopathy from BMD. In addition to normalization of the heart rate and remodeling of the left ventricle, ivabradine seems to also have a positive inotropic effect in dilated cardiomyopathy of BMD patients.

Rhabdomyolysis triggered by azithromycin.

A 17-year-old male with uneventful previous history developed generalized myalgias, exercise intolerance, and general fatigue after two dosages of azithromycin (500 mg/d) during 3 d for febrile infection. Neurologic exam revealed generally reduced tendon reflexes. Serum creatine kinase (CK) was elevated to 25000 U/L. Needle-EMG showed short and small, polyphasic motor-units and abnormal spontaneous activity, being interpreted as myositis. Azithromycin was discontinued and he was advised to avoid the fitness studio and to drink plenty of liquids. Myalgias disappeared within two days and CK continuously declined. Azithromycin may trigger rhabdomyolysis in the context of exercise and infection. Azithromycin may be myotoxic and should be prescribed with caution in exercising and infected patients.

Neurological manifestations of atrio-esophageal fistulas from left atrial ablation.

Left atrial ablation (LAAB) is carried out as an alternative treatment of atrial fibrillation refractory to conservative measures. An increasingly recognized complication of LAAB is an atrio-esophageal fistula (AEF). Neurological manifestations usually dominate the presentation of an AEF and result from cardiac embolism of thrombi, transgressed esophageal contents, or air. AEFs have been reported after LAAB in 52 patients (23 men, age 35-76 years), described in 24 publications, so far. AEFs manifest clinically on the average 17 days (3-38 days) after ablation. Neurological manifestations include embolic strokes (n = 30), seizures (n = 9), transitory-ischaemic attacks (n = 6), coma (n = 6), or psychiatric abnormalities (n = 5). Imaging studies of the cerebrum most frequently show multiple embolic strokes or air embolism. The diagnosis is made upon thoracic computed tomography with contrast media. An act of swallowing, trans-esophageal echocardiography, gastroscopy, or esophageal stenting must be avoided not to enlarge the shunt. The only expedient therapy is surgical closure of the fistula, but even then, the prognosis is poor with a mortality of 71%. AEFs should be suspected if there is a history of LAAB followed by fever, thoracic pain, postprandial cerebral strokes, seizures, coma, or confusion with a latency of days to 5 weeks after ablation. Diagnostic work-up must avoid measures, which enlarge the fistula. Treatment is surgical exclusively.

[Neurological complications of atrioesophageal fistulas: postprandial insults, epilepsy and meningitis]. / Neurologische Komplikationen atrioösophagealer Fisteln : Postprandialer Insult, Epilepsie und Meningitis.

BACKGROUND: Atrioesophageal fistulas (AEF) are a life-threatening complication of left atrial ablation for atrial fibrillation or other atrial rhythm disorders, which mostly manifest as neurological deficits. AEFs result in an overflow of esophageal contents into the left atrium with subsequent systemic embolization. RESULTS: AEFs have been reported in 40 patients, including 18 males, between 35 and 72 years of age. AEFs manifested clinically between 3 and 36 days following the ablation. The most common neurological manifestations are postprandial embolic stroke followed by epileptic seizures and meningitis. More rarely, disorders of consciousness without epilepsy or stroke, psychiatric abnormalities or cerebral air embolisms have been observed. The diagnosis is made upon thoracic computed tomography with contrast medium. Deglutation radiography, transesophageal echocardiography, gastroscopy and esophageal stenting must be absolutely avoided. The only expedient therapy is surgical cleansing of the fistula but even then the prognosis is very poor with a mortality of 63%. CONCLUSIONS: An AEF should always be considered in patients with fever, difficulties in swallowing, thoracic pain, postprandial transient ischemic attacks (TIA) or stroke, epileptic seizures, or meningitis. In the case of AEFs an ablation of atrial fibrillation in the patient history should be considered and corresponding diagnostics and treatment should be initiated immediately.

Heat-related side-effects of neurological and non-neurological medication may increase heatwave fatalities.

BACKGROUND: During the 2003 French heatwave 15,000 excess deaths were registered. One fifths died from the combination of dehydration, heatstroke, and hyperthermia and one tenth from dehydration, despite abundant water. METHODS AND RESULTS: We hypothesized that physiologic adaptation to heat was not effective in the victims attributable to side-effects of drugs (impaired thermoregulation, suppressed thirst) many of these patients were taking. This could explain why many victims died of dehydration despite availability of water. As a consequence of the global climate change heatwaves may occur more frequently and may be more intense, with a strong impact on the future selection of drugs in elderly patients. CONCLUSION: Insufficient water intake, impaired thermoregulation, and resulting death may be directly linked to the use of certain drugs, implying an immediate need for public awareness during heatwaves and for long-term strategies to mitigate the expected increase in future heatwave-related fatalities.

Prevention of embolic stroke by catheter ablation of atrial fibrillation.

BACKGROUND AND PURPOSE: Radiofrequency-catheter-ablation of atrial fibrillation is now commonly performed. Aim of this short review is to summarize questions and uncertainties concerning radiofrequency ablation of atrial fibrillation with respect to therapeutic mechanisms, long-term efficacy and stroke-prevention. RESULTS: The majority of atrial fibrillation patients is too old for radiofrequency ablation. Candidates for radiofrequency ablation belong to a subgroup with a low embolic risk. The radiofrequency ablation procedure itself may increase the embolic risk, and at present it is uncertain how long this embolic risk persists after the procedure. CONCLUSION: We doubt if radiofrequency ablation prevents embolism in atrial fibrillation.

Strategies for primary and secondary stroke prevention in atrial fibrillation.

Atrial fibrillation (AF) is the most common type of cardiac rhythm abnormality in adults, affecting 1 to 1.5% of the general population in the Western world and is the major risk factor for stroke with a fivefold risk compared with the general population. Pharmacological and nonpharmacological strategies are available for controlling recurrent or permanent AF as well as for prevention of AF. Prevention of recurrent AF is one of the best protections against AF-related stroke and reduces the prevalence of stroke by almost 25%. Antiplatelet compounds are indicated for CHAD scores 0-1 and reduce the risk of stroke from AF by 20 to 25%. For CHAD scores >1 oral anticoagulation with vitamin K antagonists is indicated and reduces the risk of stroke by 62%. Since inhibitors of coagulation factors Xa, VII , or II a have either not been clinically tested for their efficacy for prevention of stroke from AF, did not show a comparable effect to well-established drugs, or had excess side effects (idraparinux, ximelagatran), and since mechanical devices are highly questionable concerning their long-term effect, there is currently no alternative to oral anticoagulation with vitamin K antagonists as primary or secondary stroke prevention in high-risk AF patients.

Recurrent aspiration pneumonia after laparoscopic adjustable gastric banding.

Laparoscopic adjustable gastric banding is a popular therapeutic option for morbid obesity. Band slippage, pouch enlargement and esophageal dilatation are occasional late complications of this procedure. There are rare reports of recurrent aspiration after banding. We report a 44-year-old female suffering from dysphagia and aspiration pneumonia 2 years after adjustable banding. Her esophagus was dilated to 6 cm, and videocinematography showed a severe achalasia-like disorder. Withdrawal of fluid from the band should be immediate, and relieved the stomal obstruction in this patient. Aspiration pneumonia is a serious late complication, which is easily treated by deflation of the band.

Cardiac and noncardiac, particularly neuromuscular, disease with troponin-T positivity.

OBJECTIVES: Although elevated cardiac troponin T is caused by myocardial damage in the vast majority of the cases (primary cardiac causes), noncardiac disease with secondary damage to the myocardium (secondary cardiac causes) is being increasingly recognised. The present study aimed to retrospectively evaluate the frequency of primary cardiac and secondary cardiac causes of troponin-T positivity, in particular how often troponin-T positivity is associated with neuromuscular disorders. RESULTS: Of 16,944 troponin-T determinations in a secondary centre between April 2004 and April 2005, troponin T was positive in 1408 of them (8.3%). Of these, 622 were included for evaluation. Troponin-T positivity was associated with elevated creatine kinase in 54.5% and with creatinine >2 mg/dl (177 micromol/l) in 16.6% of the tests. The most frequent primary cardiac causes of troponin-T positivity were myocardial ischaemia (59%), atrial fibrillation (23%), and heart failure (22%). The most frequent secondary cardiac causes of troponin-T positivity were renal insufficiency (22%), chronic obstructive lung disease (10%), and acute stroke (4%). There was one cause for troponin-T positivity in 249 cases and more than one in 373 cases. A neurologist saw patients with troponin-T positivity in 9.5% of the cases. Troponin-T positivity was associated with a neuromuscular disorder in 6.3% of the cases. Causes of troponin-I positivity were also frequently causes of troponin-T positivity. CONCLUSIONS: Ischaemic heart disease is the most frequent cause of troponin-T positivity, followed by heart failure and renal insufficiency. Many causes previously described to be only responsible for troponin-I positivity also cause troponin-T elevation. Troponin-T positivity is frequently associated with neuromuscular disorders, most likely due to cardiac involvement of these conditions.