Arshid Azarine

Desmosomal gene analysis in arrhythmogenic right ventricular dysplasia/cardiomyopathy: spectrum of mutations and clinical impact in practice

AIMS Five desmosomal genes have been recently implicated in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) but the clinical impact of genetics remains poorly understood. We wanted to address the potential impact of genotyping. METHODS AND RESULTS Direct sequencing of the five genes (JUP, DSP, PKP2, DSG2, and DSC2) was performed in 135 unrelated patients with ARVD/C. We identified 41 different disease-causing mutations, including 28 novel ones, in 62 patients (46%). In addition, a genetic variant of unknown significance was identified in nine additional patients (7%). Distribution of genes was 31% (PKP2), 10% (DSG2), 4.5% (DSP), 1.5% (DSC2), and 0% (JUP). The presence of desmosomal mutations was not associated with familial context but was associated with young age, symptoms, electrical substrate, and extensive structural damage. When compared with other genes, DSG2 mutations were associated with more frequent left ventricular involvement (P = 0.006). Finally, complex genetic status with multiple mutations was identified in 4% of patients and was associated with more frequent sudden death (P = 0.047). CONCLUSION This study supports the use of genetic testing as a new diagnostic tool in ARVC/D and also suggests a prognostic impact, as the severity of the disease appears different according to the underlying gene or the presence of multiple mutations.

Association Between 2 Angiographic Subtypes of Renal Artery Fibromuscular Dysplasia and Clinical Characteristics

Background— Initially based on histology, the diagnosis of renal artery fibromuscular dysplasia (FMD) is now based mostly on angiographic appearance because arterial tissue samples are rarely available. This retrospective cross-sectional study aimed to assess the clinical relevance of a binary angiographic classification of FMD lesions (unifocal or multifocal) based on computed tomographic or magnetic resonance angiography. Methods and Results— Adult patients diagnosed with FMD in a single tertiary care center for hypertension management were identified by screening of electronic files. FMD lesions were reviewed and classified according to computed tomography or magnetic resonance angiography as multifocal if there were at least 2 stenoses in the same arterial segment; otherwise, they were classified as unifocal. Of 337 patients with established renal artery FMD, 276 (82%) were classified as multifocal. Patients with unifocal and multifocal lesions differed significantly in median age at diagnosis of FMD (30 and 49 years) and hypertension (26 and 40 years), sex distribution (female:male ratio, 2:1 and 5:1), initial blood pressure (157/97 and 146/88 mm Hg), current smoking (50% and 26%), prevalence of unilateral renal artery lesions (79% and 38%), presence of kidney asymmetry (33% and 10%), renal revascularization procedures (90% and 35%), and hypertension cure rates in patients who underwent revascularization (54% and 26%). Conclusions— A binary angiographic classification into unifocal or multifocal renal artery FMD is straightforward and discriminates 2 groups of patients with different clinical phenotypes.

Association of Smoking With Phenotype at Diagnosis and Vascular Interventions in Patients With Renal Artery Fibromuscular Dysplasia

The pathogenesis of fibromuscular dysplasia (FMD) remains unclear, but tobacco use is thought to be involved. This retrospective cross-sectional study aimed to evaluate smoking first as a risk factor for renal artery FMD diagnosis and second as a modifier of the clinical and radiological phenotype of this disease. We retrieved 337 adult patients diagnosed with FMD in a referral center for hypertension management, who were first individually matched to controls with essential hypertension for sex, age, systolic blood pressure, number of antihypertensive drugs, and year of visit. Smoking status and other relevant data were collected at first visit. The proportion of current smokers was higher for patients with FMD than for the controls (30% and 18%, respectively, P<0.001; odds ratio, 2.5 [95% confidence interval, 1.6–3.9]). Second, characteristics of FMD were compared between current smokers and other patients. Among patients with multifocal FMD, current smokers experienced an earlier diagnosis of hypertension (36 versus 42 years, respectively; P<0.001) and FMD (43 versus 51 years; P<0.001) than other patients, and a greater likelihood of renal artery interventions (57% versus 31%; P<0.001) and of kidney asymmetry (21% versus 4%; P=0.001). In conclusion, current smoking is associated with a higher likelihood of renal artery FMD diagnosis. Rather than a higher incidence of FMD, this may reflect a more aggressive course in smokers, who have earlier hypertension leading to increased and earlier recognition of the disease. Smoking cessation should be strongly encouraged in patients with FMD.

Rapid onset of peripheral artery disease in a chronic myeloid leukemia patient without prior arterial disorder: direct relationship with nilotinib exposure and clinical outcome

The second‐generation tyrosine kinase inhibitor (TKI) of the BCR‐ABL1 oncoprotein nilotinib used in patients with chronic myeloid leukemia is suspected to increase the risk of arterial occlusion, especially in patients with pre‐existing cardiovascular risk factors or established cardiovascular diseases. Here, we describe a case of unexpected and rapid onset of symptomatic peripheral artery disease (PAD) associated with silent stenosis of digestive and renal arteries in a nilotinib‐treated patient devoid of significant cardiovascular diseases (CVD) risk factor, prior atherosclerotic disease, or other cause of arterial damage. This is the first report to establish a direct relationship between nilotinib exposure and PAD and to reveal that arterial damage is irreversible despite rapid drug withdrawal. However, functional outcome was favorable upon rapid TKI replacement, specific cardiovascular disease management, and development of collateral arterial network.

Correspondence Between Delayed Enhancement Patterns in Multislice Computed Tomography and Magnetic Resonance Imaging in a Case of Acute Myocarditis

A 42-year-old man who was an active smoker with no significant medical history presented with severe substernal pain 5 days after acute enteritis. The examination showed mild fever, blood pressure of 113/75 mm Hg, and heart rate of 85 beats per minute. The ECG showed sinus rhythm with incomplete left bundle-branch block. Laboratory tests showed elevated levels of troponin I (23 μg/L) and C-reactive protein (104 mg/L). …

Fortuitous Discovery of Partial Uhl Anomaly in a Male Adult

We report the case of a 44-year-old man referred to our institution for suspicion of arrhythmogenic right ventricular (RV) cardiomyopathy. Both familial and personal medical histories were unremarkable, except the notion of a slight unexplored heart murmur during childhood. He decided to undergo a “40s” medical checkup. On presentation to the general practitioner, he had described a slight fatigue for 8 months without concomitant stress. Physical examination revealed no abnormality. ECG showed a type I atrioventricular block and a complete right bundle-branch block (Figure 1A). Transthoracic echocardiography showed an unusual left ventricle (LV) with a leftward curveted interventricular septum (IVS) and preserved global and segmental LV systolic function, suggestive of high systolic RV pressure or takotsubo cardiomyopathy (Figure 1B and Movie I in the online-only Data Supplement). However further analysis showed normal systolic pulmonary artery pressure and LV filling pressures. The apical 4-chamber view showed an abnormal RV with an aneurysm-like shape of the basal lateral free wall (Figure 1B and Movie II in the online-only Data Supplement) but with normal kinetics. A first cardiac magnetic resonance image showed biventricular abnormalities, particularly focused on RV wall motion, which justified additional morphological investigations. No abnormal pulmonary venous return was noticed. Invasive coronary angiogram was normal. The patient was later referred to our unit by his attending cardiologist and underwent invasive hemodynamics and biventricular contrast angiography. Cardiac index (pulmonary artery thermodilution) and biventricular volumes were normal. Blood gas content analysis disclosed an intracardiac shunt. RV angiography (Figure 2A and 2B) showed a truncated RV apex and the absence of trabeculations in the anteroapical and inferoapical zones, therefore characterized by a smooth …

Abdominal Aortic Calcifications Influences the Systemic and Renal Hemodynamic Response to Renal Denervation in the DENERHTN (Renal Denervation for Hypertension) Trial

Background The DENERHTN (Renal Denervation for Hypertension) trial confirmed the efficacy of renal denervation (RDN) in lowering daytime ambulatory systolic blood pressure when added to standardized stepped‐care antihypertensive treatment (SSAHT) for resistant hypertension at 6 months. Methods and Results This post hoc exploratory analysis assessed the impact of abdominal aortic calcifications (AAC) on the hemodynamic and renal response to RDN at 6 months. In total, 106 patients with resistant hypertension were randomly assigned to RDN plus SSAHT or to the same SSAHT alone (control group). Total AAC volume was measured, with semiautomatic software and blind to randomization, from the aortic hiatus to the iliac bifurcation using the prerandomization noncontrast abdominal computed tomography scans of 90 patients. Measurements were expressed as tertiles. The baseline‐adjusted difference in the change in daytime ambulatory systolic blood pressure from baseline to 6 months between the RDN and control groups was −10.1 mm Hg (P=0.0462) in the lowest tertile and −2.5 mm Hg (P=0.4987) in the 2 highest tertiles of AAC volume. Estimated glomerular filtration rate remained stable at 6 months for the patients in the lowest tertile of AAC volume who underwent RDN (+2.5 mL/min per 1.73 m2) but decreased in the control group (−8.0 mL/min per 1.73 m2, P=0.0148). In the 2 highest tertiles of AAC volume, estimated glomerular filtration rate decreased similarly in the RDN and control groups (P=0.2640). Conclusions RDN plus SSAHT resulted in a larger decrease in daytime ambulatory systolic blood pressure than SSAHT alone in patients with a lower AAC burden than in those with a higher AAC burden. This larger decrease in daytime ambulatory systolic blood pressure was not associated with a decrease in estimated glomerular filtration rate. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01570777.

Recurrent tamponade and aortic dissection in syphilis.

Syphilitic cardiovascular disease has been described since the 19th century, mainly on autopsy series. Major clinical manifestations are aortic aneurysm, aortic insufficiency, and coronary ostial stenosis. The diagnosis of syphilitic cardiovascular disease is based mainly on positive serologic tests and overt clinical manifestations. We present here a rare and unusual clinical presentation of a tertiary syphilis with recurrent tamponade and type B aortic dissection, whose positive diagnosis was made by polymerase chain reaction on pericardial fluid analysis.

Different focal delayed gadolinium-enhancement patterns using cardiac magnetic resonance in a case of diffuse giant cell myocarditis

A 17-year-old man was admitted for new onset of fatigue with dyspnoea. He did not present fever or a recent history of flu-like symptoms. The results of the physical examination and ECG were unremarkable except for a sinus tachycardia at 116 b.p.m. Echocardiography demonstrated severe global hypokinesia of both ventricles with left ventricular ejection fraction (LVEF) of 10%. Laboratory tests revealed a troponin …

Inverted stress (Takotsubo) cardiomyopathy following caesarean section: insights from cardiac magnetic resonance.

a Cardiovascular Imaging Department, AP-HP, Hopital Europeen Georges Pompidou, Universite Paris Descartes, Paris, France b Division of Cardiology, AP-HP, Hopital Europeen Georges Pompidou, Universite Paris Descartes, Paris, France c Division of Cardiology, AP-HP, Hopital Necker-Enfants Malades, Universite Paris Descartes, Paris, France d INSERM U678, Universite Pierre et Marie Curie, Paris, France