Predictors of Fabry disease in patients with hypertrophic cardiomyopathy: How to guide the diagnostic strategy?

BACKGROUND: Fabry disease (FD) is a treatable cause of hypertrophic cardiomyopathy (HCM). We aimed to determine the independent predictors of FD and to define a clinically useful strategy to discriminate FD among HCM. METHODS: Multicenter study including 780 patients with the ESC definition of HCM. FD screening was performed by enzymatic assay in males and genetic testing in females. Multivariate regression analysis identified independent predictors of FD in HCM. A discriminant function analysis defined a score based on the weighted combination of these predictors. RESULTS: FD was found in 37 of 780 patients with HCM (4.7%): 31 with p.F113L mutation due to a founder effect; and 6 with other variants (p.C94S; p.M96V; p.G183V; p.E203X; p.M290I; p.R356Q/p.G360R). FD prevalence in HCM adjusted for the founder effect was 0.9%. Symmetric HCM (OR 3.464, CI95% 1.151-10.430), basal inferolateral late gadolinium enhancement (LGE) (OR 10.677, CI95% 3.633-31.380), bifascicular block (OR 10.909, CI95% 2.377-50.059) and ST-segment depression (OR 4.401, CI95% 1.431-13.533) were independent predictors of FD in HCM. The score ID FABRY-HCM [-0.729 + (2.781xBifascicular block) + (0.590xST depression) + (0.831xSymmetric HCM) + (2.130xbasal inferolateral LGE)] had a negative predictive value of 95.8% for FD, with a cut-off of 1.0, meaning that, in the absence of both bifascicular block and basal inferolateral LGE, FD is a less probable cause of HCM, being more appropriate to perform HCM gene panel than targeted FD screening. CONCLUSION: FD prevalence in HCM was 0.9%. Bifascicular block and basal inferolateral LGE were the most powerful predictors of FD in HCM. In their absence, HCM gene panel is the most appropriate step in etiological study of HCM.

Unusual place unusual number.

Cardiac papillary fibroelastoma is a rare, benign cardiac tumor. It often arises from the valvular endocardium and is usually solitary. Nonvalvular location is rare and even more rare is the presentation as multiple masses. A 71-year-old female patient was referred for echocardiographic evaluation due to progressive fatigue. The presence of multiple left atrial masses was observed on echocardiographic evaluation. The patient was treated surgically for the prevention of embolic complications, and the histologic diagnosis of multiple nonvalvular papillary fibroelastoma was made. This case highlights the need to consider this unusual location and presentation for this type of tumor.

Drug Withdrawal Due to Safety: A Review of the Data Supporting Withdrawal Decision.

INTRODUCTION: Several drugs were withdrawn from the market due to safety. OBJECTIVE: The aim of this study was to describe data supporting drug withdrawal from the market due to safety reasons in countries belonging to the World Health Organization. METHODS: We analyzed drugs withdrawn from the market between 1990 and 2010. All medicine agencies of the countries belonging to the Program for International Drug Monitoring of the World Health Organization were contacted. To complete data, Medline, reference books and available drug databases were also searched. Information sources on which authorities based their withdrawal were categorized and the average time between the first date of exposure and withdrawal was calculated and stratified. RESULTS: A total of 133 drugs that met the inclusion/exclusion criteria were withdrawn from the market due to safety reasons in the period reviewed (1990 - 2010). Hepatotoxicity (n=36, 27.1%), cardiac disorders (n=25, 18.8%), hypersensitivity (n=17, 12.8%) and nephrotoxicity (n=14, 9.8%) were the major reasons responsible for 69.2% of all drugs withdrawn. In most cases, Information Sources for drug withdrawal were spontaneous reports and/or case reports (n=86, 64.7%), followed by clinical trials (n=24, 18.0%). The average time between the introduction of a drug and its withdrawal due to safety reasons was 20.3 years (SD±13.8). CONCLUSION: According to available and published evidence, there is no gold standard to identify risks associated with drug exposure. These findings strengthen the role of different information sources within the drug safety review process.

Hemodynamic differences among hypertensive patients with and without heart failure using impedance cardiography.

BACKGROUND: Impedance cardiography is a reliable, well-tolerated, and non-invasive method used to obtain hemodynamic measurements and could potentially be useful in heart failure (HF) diagnosis, hemodynamic monitoring of critically ill patients, and help in the choice of antihypertensive therapy. The objective of this study was to determine the differences between hemodynamic parameters in a study population of hypertensive patients with and without HF, using impedance cardiography. METHODS: A case-control study was designed and named the TARGET study. Participants were enrolled in two study groups: control group C, hypertensive patients without HF and the HF group, hypertensive patients with HF. A descriptive analysis was carried out to characterize the sample and differences in continuous variables were tested for statistical significance by independent sample t test. RESULTS: The study included 102 hypertensive outpatients. The control group consisted of 77 individuals (58.4% males; mean age 63.9 ± 12.5 years old) and the HF group consisted of 25 individuals (44.0% males; mean age 74.2 ± 8.7 years old). The mean Cardiac Index (CI) was 2.70 ± 1.02 L.min.m-2 (2.89 ± 1.04 versus 2.12 ± 0.70; p < 0.001), mean Stroke Index (SI) was 35.5 ± 14.7 mL.m-2 (37.7 ± 15.2 versus 28.5 ± 10.8; p = 0.006), mean Ejection Phase Contractility Index (EPCI) was 33.7 ± 12.7 1000 s-2 (35.8 ± 13.1 versus 27.2 ± 9.2; p = 0.003), mean Inotropic State Index (ISI) was 74.3 ± 28.2 100 s-2 (78.8 ± 28.9 versus 60.6 ± 20.7; p = 0.005), and mean Left Stroke Work Index (LSWI) was 51.3 ± 23.1 g.min.m-2 (55.4 ± 23.5 versus 38.9 ± 16.6; p = 0.002). CONCLUSIONS: In this study, hypertensive patients with HF had significantly lower values of blood flow parameters, contractility, and left work indices compared with hypertensive patients without HF. These differences reflected the incorrect hemodynamic pattern (mostly hypodynamic) of these patients. Impedance cardiography (ICG) seems to be an adequate method to reflect these differences.

L-TRUST: Long-term risk of cancer in patients under statins therapy. A systematic review and meta-analysis.

INTRODUCTION: Statins are widely prescribed drugs with established efficacy in primary and secondary prevention of cardiovascular events. Although they are mostly well tolerated, several authors have been emphasizing that the statins' safety profile is not totally clarified especially when considering risk of cancer in patients with long-term exposure to statins. This meta-analysis was aimed at evaluating the risk of cancer in patients with prolonged exposure to statins. METHODS: Medline, Cochrane library, and clinicaltrials.gov were searched in order to identify studies with a minimum average follow-up of 10 years of exposure to statins and a cancer-related outcome reported. Relative risk (RR) of the primary outcomes and the combined effect was presented using a random-effects model. In the selected randomized control trials (RCT), statin exposure was compared with placebo, and in the selected observational studies, it was compared with no exposure to statins. RESULTS: We retrieved 1627 studies, of which 15 full-papers were included for final review, five RCT, two cohort studies (CSs), and eight case-control studies (CCs), representing a total of 358 544 patients. Five RCT, two cohort studies (CSs), and eight case-control studies (CCs). No significant differences were found regarding risk of cancer occurrence (RR = 1.08, 0.96-1.21) or cancer mortality (RR = 0.91, 0.80-1.04) due to long-term statin exposure. Regarding all-cause mortality, a protective effect was found (RR = 0.93, 0.90-0.97). CONCLUSIONS: According to available and published evidence, statins are not associated with an increased risk of cancer after prolonged exposure. These findings strengthen the role of statins in the primary and secondary prevention of cardiovascular events.

Screening for Fabry disease in patients with left ventricular noncompaction.

INTRODUCTION AND AIM: It is unclear whether left ventricular noncompaction (LVNC) is a distinct cardiomyopathy or a morphologic manifestation of different cardiomyopathies. We previously reported a case of LVNC in a Fabry disease (FD) patient, but it remains to be clarified whether LVNC is a cardiac manifestation of FD, a coincidental finding or an overdiagnosis, which has major therapeutic implications. This study aims to determine the prevalence of FD among patients with LVNC. METHODS: We performed a retrospective study including all patients diagnosed with LVNC in eight hospital centers. Diagnosis of LVNC was based on at least one echocardiographic or cardiac magnetic resonance criterion. FD screening was performed by combined enzyme and genetic testing. RESULTS: The study included 78 patients diagnosed with LVNC based on the Jenni (84.6%), Stöllberger (46.2%), Chin (21.8%), Petersen (83.8%) and Jacquier (16.2%) criteria. Left ventricular systolic dysfunction was present in 48.7%. Heart failure was found in 60.3%, ventricular dysrhythmias in 21.6% and embolic events in 11.5%. FD screening found no additional cases among patients with LVNC, besides the previously described case. CONCLUSION: No additional FD cases were found among patients with LVNC, which argues against the hypothesis that LVNC is a cardiac manifestation of FD.

Vasculitis of small and large vessels, a casual association?

The authors report a case of a 69-year-old man with idiopathic leukocytoclastic cutaneous vasculitis. For three years, the lesions recurred with progressive worsening and were associated with systemic manifestations of low-grade fever, weight loss and raised inflammatory markers. The patient latter presented a 6th cranial nerve involvement, raising the concern of a possible systemic vasculitis, which was latter evidenced by the development of deep vein thrombosis and angina pectoris. The treatment of the patient witch based on the decreasing of inflammatory activity, by using effective immunosuppressive therapy, with lower toxicity is more important than identifying the type of the vasculitis. This case illustrates the importance of awareness for the systemic involvement that can occur in up to 50% of patients with leukocytoclastic cutaneous vasculitis.

Rectal ulcer due to Kayexalate deposition - an unusual case

SUMMARY Sodium polystyrene sulfonate (PSP) or Kayexalate is a cation-exchange resin, widely used in the management of hyperkalaemia due to renal disease. A rare, yet potentially dangerous, adverse event related to sodium polystyrene sulfonate use is intestinal mucosal injury, especially in the colon. The injury to the gastrointestinal mucosa can range from mild and superficial to wall necrosis and bowel perforation. The mechanism that leads to mucosal damage remains unclear. However, it is believed that sorbitol, commonly given to counteract PSP's tendency to cause constipation, may play an important role in the development of gastrointestinal injury. Other potential risk factors are uraemia or end-stage renal disease, hemodynamic instability, solid organ transplantation, postoperative status and concomitant opioid administration. The authors present a case of diarrhoea and haematochezia after the administration of PSP without sorbitol, in a patient with hyperkalaemia due to acute kidney injury, in the absence of other risk factors. A colonoscopy was performed and revealed a rectal ulcer which histological findings were suggestive of mucosal injury due to Kayexalate deposition. This case supports the concept that this widely used drug can itself, without sorbitol, cause injury to the gastrointestinal wall. Even though this is a rare adverse effect, the widespread use of this medication may put a large population at risk.

RESUMO O polistireno sulfonato de sódio (PSP) ou kayexalato é uma resina de troca iônica, amplamente usada no tratamento da hipercalemia associada à doença renal. Um efeito adverso raro, mas potencialmente grave, dessa terapêutica é a agressão à parede do trato gastrointestinal, principalmente ao nível do cólon, que pode ser ligeira e superficial ou culminar em necrose e perfuração intestinal. O mecanismo pelo qual o PSP lesa a mucosa intestinal não é totalmente conhecido. Contudo, pensa-se que o sorbitol, frequentemente administrado em simultâneo para contrabalançar o efeito obstipante do PSP, possa ter um papel preponderante no desenvolvimento de lesão gastrointestinal. Outros potenciais fatores de risco são a presença de uremia ou doença renal em estágio terminal, instabilidade hemodinâmica, pós-operatório, pós-transplante renal e a administração concomitante de opioides. Os autores descrevem um caso de diarreia e hematoquesias após a administração de PSP sem sorbitol, numa paciente com hipercalemia secundária a lesão renal aguda, sem outros fatores de risco para o desenvolvimento desse efeito adverso. A investigação etiológica com colonoscopia revelou a presença de uma úlcera retal, cujo estudo histológico foi compatível com lesão por deposição de cristais de kayexalato. Este relato incomum reforça o conceito de que este fármaco de uso frequente, mesmo na ausência de sorbitol, pode ser lesivo para a mucosa intestinal. Assim, e apesar de este ser um efeito adverso raro, a utilização difundida do PSP coloca uma vasta população em risco.

Vasculitis of small and large vessels, a casual association?

SUMMARY The authors report a case of a 69-year-old man with idiopathic leukocytoclastic cutaneous vasculitis. For three years, the lesions recurred with progressive worsening and were associated with systemic manifestations of low-grade fever, weight loss and raised inflammatory markers. The patient latter presented a 6th cranial nerve involvement, raising the concern of a possible systemic vasculitis, which was latter evidenced by the development of deep vein thrombosis and angina pectoris. The treatment of the patient witch based on the decreasing of inflammatory activity, by using effective immunosuppressive therapy, with lower toxicity is more important than identifying the type of the vasculitis. This case illustrates the importance of awareness for the systemic involvement that can occur in up to 50% of patients with leukocytoclastic cutaneous vasculitis.

RESUMO Os autores reportam um caso de vasculite leucocitoclástica recidivante num homem de 69 anos. Durante cerca de três anos as lesões cutáneas de vasculite leucocitoclástica reapareceram periodicamente, acompanhando-se sempre de um quadro sistêmico caracterizado por febrícula, perda de peso e astenia, assim como aumento de novo dos parâmetros inflamatórios. O aparecimento de parésia do sexto par craniano no decurso de uma dessas recorrências cutâneas levantou a hipótese de estarmos perante uma vasculite mais agressiva, com envolvimento extracutâneo. Esse envolvimento sistêmico foi novamente evidente com aparecimento de angina pectoris e trombose venosa profunda. Atualmente, mais do que a identificação do tipo de vasculite, a abordagem dos doentes com essa patologia assenta na cessação da atividade inflamatória recorrendo a terapêutica imunossupressora eficaz, com a menor toxicidade possível. Destacamos a importância da vigilância do componente sistêmico, que pode ocorrer até 50% na vasculite leucocitoclástica cutânea.

Rectal ulcer due to Kayexalate deposition - an unusual case.

Sodium polystyrene sulfonate (PSP) or Kayexalate is a cation-exchange resin, widely used in the management of hyperkalaemia due to renal disease. A rare, yet potentially dangerous, adverse event related to sodium polystyrene sulfonate use is intestinal mucosal injury, especially in the colon. The injury to the gastrointestinal mucosa can range from mild and superficial to wall necrosis and bowel perforation. The mechanism that leads to mucosal damage remains unclear. However, it is believed that sorbitol, commonly given to counteract PSP's tendency to cause constipation, may play an important role in the development of gastrointestinal injury. Other potential risk factors are uraemia or end-stage renal disease, hemodynamic instability, solid organ transplantation, postoperative status and concomitant opioid administration. The authors present a case of diarrhoea and haematochezia after the administration of PSP without sorbitol, in a patient with hyperkalaemia due to acute kidney injury, in the absence of other risk factors. A colonoscopy was performed and revealed a rectal ulcer which histological findings were suggestive of mucosal injury due to Kayexalate deposition. This case supports the concept that this widely used drug can itself, without sorbitol, cause injury to the gastrointestinal wall. Even though this is a rare adverse effect, the widespread use of this medication may put a large population at risk.

Linfadenite recorrente. Caso clínico / Recurrent lymphadenitis. Case report

A imunodeficiência de variável comum é uma imunodeficiência primária de apresentação heterogênea, consistindo em um défice em imunoglobulinas. É caracterizada por infeções de repetição e predisposição para doenças autoimunes, granulomatosas e neoplásicas. Os autores apresentam o caso clínico de um doente com imunodeficiência comum variável manifestada por infeções cutâneas de repetição e linfadenite recorrente. Este caso tem como objetivo alertar para os aspetos clínicos desta imunodeficiência, a fim de permitir seu diagnóstico precoce, evitando-se prognósticos desfavoráveis.(AU)

Common variable immunodeficiency is a primary immunodeficiency with a heterogeneous presentation, characterized by decreased immunoglobulin levels. It is characterized by recurrent infections, predisposition to autoimmune, granulomatous and neoplastic diseases. The authors report a case of a patient with common variable immunodeficiency and history of skin infections and recurrent lymphadenitis. This case report aims to draw the attention to the clinical aspects of this immunodeficiency, in order to promote an early diagnosis, avoiding poor outcomes.(AU)

Multiple drug exposure as a risk factor for the seriousness of adverse drug reactions.

AIM: The aim of the present study was to validate the hypothesis that multiple drug exposure is an independent risk factor for serious adverse drug reactions (ADRs). BACKGROUND: Adverse drug reactions (ADRs) are an important cause of iatrogenic disease, the majority being preventable. Multiple drug exposure, ageing and female gender have been identified as important risk factors for an increased incidence of ADRs. METHOD: ADR reports received by the central Portugal Regional Pharmacovigilance Unit, between January 2001 and December 2009, were studied. RESULTS: Nearly half (47.4%) of ADRs reports were considered serious, from which 66.7% reported multiple drug exposure (mean 3.07 ± 2.2; maximum 13). After adjusting for gender, simultaneous exposure to three or more drugs was significantly associated with an increased risk of serious ADRs [odds ratio (OR) 1.23; 95% confidence interval (CI) 1.02-1.51]. CONCLUSIONS: The present results support that multiple drug exposure is an independent risk factor for serious ADRs. Such findings are of importance in both medicines benefit/risk ratio evaluations and patient safety monitoring. IMPLICATIONS FOR NURSING MANAGEMENT: A new level of nursing involvement is needed in both the detection of ADRs and prevention of serious outcomes, particularly in high-risk patients.