Róbert Sepp

Five-year experience with transradial coronary angioplasty in ST-segment-elevation myocardial infarction

BACKGROUND AND PURPOSE Percutaneous coronary intervention (PCI) via radial approach has been shown to be an alternative to femoral approach in emergency cases; however, its feasibility has been questioned. This single-center study was performed to compare the outcomes and complication rates between transradial (TR) and transfemoral (TF) PCI in ST-segment-elevation myocardial infarction (STEMI). METHODS AND MATERIALS The clinical and angiographic data of 582 consecutive STEMI patients treated with PCI between 2001 and 2006 were evaluated in a retrospective study. Forty-three patients were excluded from the present study due to cardiogenic shock or rescue PCI. Patients (n=539) were categorized into the TR group (n=167) or the TF group (n=372), and several parameters were evaluated to assess the advantages and drawbacks of TR access: access-site crossover, rate of access-site complications, procedure time, fluoroscopy time, X-ray area dose, major adverse cardiac events (MACE) at 1 month, and consumption of angioplasty equipment. RESULTS In the TR group, the crossover rate to femoral access was 5%, while in the TF group, it was 0.8% (P<.05). There was a significant difference, in both major and minor access-site complications, between the TR group and the TF group (0% vs. 5%, P<.05, and 4% vs. 9%, P<.05, respectively). Consumption of angioplasty equipment proved to be the same for the two groups. The MACE rate was 4% in the TR group and 11% in the TF group (P<.05). CONCLUSIONS Our results suggest that the TR approach is a safe and effective way to treat STEMI; furthermore, site-related complications are less common with this approach.

Three-dimensional speckle tracking echocardiography allows detailed evaluation of left atrial function in hypertrophic cardiomyopathy--insights from the MAGYAR-Path Study.

Hypertrophic cardiomyopathy (HCM) represents a generalized myopathic process affecting both ventricular and atrial myocardium. Reduced left atrial (LA) function was demonstrated in HCM by different methods. Three‐dimensional (3D) speckle tracking echocardiography (STE) has just been introduced for the evaluation of LA. This study was designed to compare 3DSTE‐derived LA volumetric and strain parameters in HCM with healthy controls.

Long-term prognostic value of coronary flow velocity reserve in patients with hypertrophic cardiomyopathy : 9-year follow-up results from SZEGED study

Reduction in coronary flow velocity reserve (CFR) is a recognized feature in hypertrophic cardiomyopathy (HCM). We sought to assess the long-term prognostic value of CFR by pulsed-wave Doppler transesophageal echocardiography (TEE) in HCM patients. The study comprised 20 patients with typical features of HCM. The patients were enrolled in 1999. All patients underwent a standard transthoracic echo-Doppler study to evaluate left ventricular function and a stress vasodilator TEE study to evaluate CFR. The success rate of follow-up was 18 out of 20 (90%). During a mean follow-up of 90 ± 24 months, four patients suffered cardiovascular death (2 sudden cardiac deaths and 2 strokes). The other seven patients underwent invasive procedures (coronary angiography, implantable cardioverter defibrillator implantation, percutaneous transluminal septal myocardial ablation) or showed cerebrovascular events. Using receiver operator characteristic analysis, CFR < 2.35 was a significant predictor for cardiovascular event-free survival (sensitivity 91%, specificity 71%, area under the curve 74%, P = 0.05). Multivariable regression analysis showed that only CFR (hazard ratio (HR) 4.21, P < 0.05) was an independent predictor of cardiovascular event-free survival. Despite the relatively small number of patients involved in the study, results could suggest that CFR should be considered as an independent predictor for future cardiovascular events in HCM patients. However, further studies with larger HCM patient populations are warranted.

Hypertrophic Cardiomyopathy Is Associated with Abnormal Echocardiographic Aortic Elastic Properties and Arteriograph‐Derived Pulse‐Wave Velocity

Objective: Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease and defined by the presence of unexplained left ventricular hypertrophy (LVH). Vascular alterations are frequently associated with HCM including microvascular and/or peripherial endothelial dysfunction. This study was designed to evaluate echocardiographic ascending aortic elastic properties and arteriograph‐derived pulse‐wave velocity (PWV) and augmentation index (Aix) in HCM. Methods: This study comprised 38 patients with typical features of HCM. Their results were compared to 20 hypertensive patients with LVH and 23 controls. Systolic and diastolic ascending aortic diameters were recorded in M‐mode at a level of 3 cm above the aortic valve from a parasternal long‐axis view. The following echocardiographic aortic elastic properties were measured from aortic data and forearm blood pressure values: aortic strain, distensibility, and stiffness index. Arteriograph‐derived PWV and AIx were also measured. Results: Aortic stiffness index (18.4 ± 17.6 vs. 6.88 ± 3.63, P < 0.05), PWV (9.44 ± 4.08 vs. 7.97 ± 1.20 m/sec, P < 0.05) and Aix (‐24.9 ± 32.6 vs. –41.4 ± 24.3, P < 0.05) were increased, while aortic strain (0.061 ± 0.053 vs. 0.100 ± 0.059, P < 0.05) and aortic distensibility (1.94 ± 1.68 cm2/dynes 10−6 vs. 3.08 ± 1.77 cm2/dynes 10−6, P < 0.05) were decreased in HCM patients compared to controls. Aortic elastic properties of hypertensive patients with LVH showed similar alterations to HCM patients. Conclusions: Abnormal echocardiographic aortic elastic properties and arteriograph‐derived PWV and Aix could be demonstrated in HCM patients compared to matched controls. (Echocardiography 2011;28:848‐852)

Subclinical skeletal muscle abnormalities in patients with hypertrophic cardiomyopathy and their relation to clinical characteristics.

BACKGROUND Some mutations of cardiac sarcomeric proteins causing hypertrophic cardiomyopathy (beta-myosin heavy chain) are associated with skeletal muscle fiber dysfunction, while subclinical skeletal myopathy can be diagnosed by electromyography (EMG) in a substantial proportion of hypertrophic cardiomyopathy patients. METHODS In 49 consecutive, unrelated patients with hypertrophic cardiomyopathy, conventional EMG of deltoid, vastus lateralis, tibialis anterior and soleus muscles was performed. No patient had clinically detectable muscle weakness. We compared the clinical and echocardiographic characteristics between patients with normal and patients with myopathic EMG. RESULTS Myopathic EMG findings were demonstrated in 13 patients (26.5%), 26 patients (53.1%) had normal findings and 10 patients (20.4%) had indeterminate recordings. There was no significant difference in mean age, maximum wall thickness, left ventricular fraction shortening, NYHA class, the existence of left ventricular outflow tract obstruction, syncope, or the occurrence of nonsustained ventricular tachycardia in the Holter recording among the three groups. Comparison between the myopathic and the normal group revealed that nine patients from the latter (34.6%) had a positive history of sudden death in the family, whereas no patient had such a history in the former group (P=0.015). CONCLUSION The higher prevalence of a family history of sudden death in patients with normal EMG, although not thoroughly explained by our data, may reflect differences in the genetic substrate produced by the higher prevalence of high-risk mutations that are not expressed in skeletal muscle (e.g. troponin T). Further evaluation in genotyped patients is warranted.

Short-term beat-to-beat variability of the QT interval is increased and correlates with parameters of left ventricular hypertrophy in patients with hypertrophic cardiomyopathy

Stratification models for the prediction of sudden cardiac death (SCD) are inappropriate in patients with hypertrophic cardiomyopathy (HCM). We investigated conventional electrocardiogram (ECG) repolarization parameters and the beat-to-beat short-term QT interval variability (QT-STV), a new parameter of proarrhythmic risk, in 37 patients with HCM (21 males, average age 48 ± 15 years). Resting ECGs were recorded for 5 min and the frequency corrected QT interval (QTc), QT dispersion (QTd), beat-to-beat short-term variability of QT interval (QT-STV), and the duration of terminal part of T waves (Tpeak-Tend) were calculated. While all repolarization parameters were significantly increased in patients with HCM compared with the controls (QTc, 488 ± 61 vs. 434 ± 23 ms, p < 0.0001; QT-STV, 4.5 ± 2 vs. 3.2 ± 1 ms, p = 0.0002; Tpeak-Tend duration, 107 ± 27 vs. 91 ± 10 ms, p = 0.0015; QTd, 47 ± 17 vs. 34 ± 9 ms, p = 0.0002), QT-STV had the highest relative increase (+41%). QT-STV also showed the best correlation with indices of left ventricular (LV) hypertrophy, i.e., maximal LV wall thickness normalized for body surface area (BSA; r = 0.461, p = 0.004) or LV mass (determined by cardiac magnetic resonance imaging) normalized for BSA (r = 0.455, p = 0.015). In summary, beat-to-beat QT-STV showed the most marked increase in patients with HCM and may represent a novel marker that merits further testing for increased SCD risk in HCM.

Identification of a Novel GLA Gene Mutation, p.Ile239Met, in Fabry Disease With a Predominant Cardiac Phenotype

Fabry disease (FD) is an X-linked inherited lysosomal storage disorder caused by mutations in the GLA gene, encoding for the enzyme α-galactosidase A. Although hundreds of mutations in the GLA gene have been described, many of them are variants of unknown significance. Here we report a novel GLA mutation, p.Ile239Met, identified in a large Hungarian three-generation family with FD. A 69 year-old female index patient with a clinical history of renal failure, hypertrophic cardiomyopathy, and 2nd degree AV block was screened for mutation in the GLA gene. Genetic screening identified a previously unreported heterozygous mutation in exon 5 of the GLA gene (c.717A>G; p.Ile239Met). Family screening indicated that altogether 6 family members carried the mutation (5 females, 1 male, average age: 55 ± 16 years). Three family members, including the index patient, manifested the cardiac phenotype of hypertrophic cardiomyopathy, while two other family members were diagnosed with left ventricular hypertrophy. Taking affection status as the presence of hypertrophic cardiomyopathy, left ventricular hypertrophy or elevated lyso-Gb3 levels, all affected family members carried the mutation. Linkage analysis of the family gave a two-point LOD score of 2.01 between the affection status and the p.Ile239Met GLA mutation. Lyso-Gb3 levels were elevated in all carrier family members (range: 2.4-13.8 ng/mL; upper limit of normal +2STD: ≤ 1.8 ng/mL). The GLA enzyme level was markedly reduced in the affected male family member (< 0.2 µmol/L/hour; upper limit of normal ± 2STD: ≥ 2.6 µmol/L/hour). We conclude that the p. Ile239Met GLA mutation is a pathogenic mutation for FD associated with predominant cardiac phenotype.

Timothy syndrome 1 genotype without syndactyly and major extracardiac manifestations

Timothy syndrome 1 (TS1) is a rare genetic disorder characterized by multisystem abnormalities including QT prolongation, congenital heart defects, facial dysmorphism, episodic hypoglycemia, and neurological symptoms. A morphological hallmark of TS1 is syndactyly, present in all cases. TS1 is caused by the canonical p.Gly406Arg mutation in the alternatively spliced exon 8A in the CACNA1C gene, encoding for the main cardiac L‐type calcium channel. A variant case of TS1 is reported. The proband had intermittent fetal bradycardia with heart rate of 72 bpm. On the first day of life bradycardia due to 2:1 atrioventricular (AV) block and marked QTc prolongation of 600 ms was noted. On medical therapy with propranolol and mexiletine 1:1 AV conduction returned with QTc prolongation of 470–580 ms. The patient lacked other extracardiac manifestations, most importantly syndactyly, neurological complications or autism. On genetic analysis, the canonical TS1 causing mutation, p.Gly406Arg in exon 8A of the CACNA1C gene was detected. The CACNA1C p.Gly406Arg variant was not present in the parents, but was detected in different DNA samples of the index patient. Our case highlight further phenotypic variability in TS. Most importantly, it underlines that the lack of syndactyly does not exclude the presence of a TS1 genotype.

Different patterns of left ventricular rotational mechanics in cardiac amyloidosis—results from the three-dimensional speckle-tracking echocardiographic MAGYAR-Path Study

Cardiac amyloidosis (CA) is an infiltrative disease primarily caused by extracellular tissue deposition of amyloid fibrils in the myocardial interstitium. The aim of the present study was to examine left ventricular (LV) rotational mechanics in biopsy-proven CA by three-dimensional (3D) speckle-tracking echocardiography (STE). Ten patients (65.3±11.5 years, 6 males) with CA entered the study. The mean basal LV rotations were 0.3±3.8°, while mean apical LV rotations proved to be 7.0±3.3°. LV basal and apical rotations were in the same counterclockwise direction in 6 out of 10 CA patients demonstrating near absence of LV twist [LV rigid body rotation (RBR)]. Apico-basal difference was near 3 or less degrees in three patients with LV-RBR, and 6-10 degrees in the other three subjects with LV-RBR. One another patient showed normal rotational mechanics, while two patients had significant hyporotations and one had significant hyperrotations in normal directions. To conclude with, different patterns of LV rotational mechanics could be demonstrated in CA. LV RBR, the near absence of LV twist seems to be a frequent phenomenon in CA.

Left atrial dysfunction in light-chain cardiac amyloidosis and hypertrophic cardiomyopathy – A comparative three-dimensional speckle-tracking echocardiographic analysis from the MAGYAR-Path Study

INTRODUCTION While cardiac amyloidosis (CA) is a rare systemic disease characterized by extracellular deposition of protein-derived fibrils, hypertrophic cardiomyopathy (HCM) is histopathologically characterized by myocyte hypertrophy and disarray, interstitial fibrosis, and small intramural coronary arteriole dysplasia. The aim of the present study was to compare left atrial (LA) volumetric and functional characteristics between light-chain (AL) CA and HCM by three-dimensional (3D) speckle-tracking echocardiography (STE). METHODS The AL-CA group initially consisted of 17 patients with AL-CA, but one patient was excluded due to inadequate image quality, and so the study population consisted of 16 patients (mean age: 64.0±9.6 years, five men). Their results were compared with data on 20 age-matched HCM patients (mean age: 59.8±5.2 years, 10 men) and on 16 age-matched healthy controls (mean age: 58.2±7.2 years, six men). Complete two-dimensional Doppler echocardiography and 3D-STE were performed in all cases. RESULTS Significantly increased LA volumes were observed in both AL-CA and HCM compared with the control group. Only active atrial emptying fraction was found to be significantly reduced in AL-CA patients compared to controls. Peak global and mean segmental circumferential, longitudinal and area strains showed significant reductions in AL-CA patients compared with controls, but only peak mean segmental longitudinal strain differed significantly between HCM patients and controls. While no differences were demonstrated in global and mean segmental strain at atrial contraction between HCM patients and controls, AL-CA patients showed reductions in certain strain parameters compared to controls and HCM patients. CONCLUSIONS Different patterns of LA functional characteristics were demonstrated in AL-CA and HCM patients by 3D-STE.