Antagonism of contractile forces in left ventricular hypertrophy: a diagnostic challenge for better pathophysiological and clinical understanding.

Cardiac function is characterised by haemodynamic parameters in the clinical scenario. Due to recent development in imaging techniques, the clinicians focus on the quantitative assessment of left ventricular size, shape and motion patterns mostly analysed by echocardiography and cardiac magnetic resonance. Because of the physiologically known antagonistic structure and function of the heart muscle, the effective performance of the heart remains hidden behind haemodynamic parameters. In fact, a smaller component of oblique transmural netting of cardiac muscle fibres simultaneously engenders contracting and dilating force vectors, while the predominant mass of the tangentially aligned fibres only acts in one direction. In case of hypertrophy, an increased influence of the dilating transmural fibre component might counteract systolic wall thickening, thereby counteract cardiac output. A further important aspect is the response to inotropic stimulation that is different for the tangentially aligned fibre component in comparison to the transmural component. Both aspects highlight the importance to integrate the analysis of intramural fibre architecture into the clinical cardiac diagnostics.

Six sequence variants on chromosome 9p21.3 are associated with a positive family history of myocardial infarction: a multicenter registry.

BACKGROUND: Recent genome-wide association studies have identified several genetic loci linked to coronary artery disease (CAD) and myocardial infarction (MI). The 9p21.3 locus was verified by numerous replication studies to be the first common locus for CAD and MI. In the present study, we investigated whether six single nucleotide polymorphisms (SNP) rs1333049, rs1333040, rs10757274, rs2383206, rs10757278, and rs2383207 representing the 9p21.3 locus were associated with the incidence of an acute MI in patients with the main focus on the familial aggregation of the disease. METHODS: The overall cohort consisted of 976 unrelated male patients presenting with an acute coronary syndrome (ACS) with ST-elevated (STEMI) as well as non-ST-elevated myocardial infarction (NSTEMI). Genotyping data of the investigated SNPs were generated and statistically analyzed in comparison to previously published findings of matchable control cohorts. RESULTS: Statistical evaluation confirmed a highly significant association of all analyzed SNP's with the occurrence of MI (p<0.0001; OR: 1.621-2.039). When only MI patients with a positive family disposition were comprised in the analysis a much stronger association of the accordant risk alleles with incident disease was found with odds ratios up to 2.769. CONCLUSIONS: The findings in the present study confirmed a strong association of the 9p21.3 locus with MI particularly in patients with a positive family history thereby, emphasizing the pathogenic relevance of this locus as a common genetic cardiovascular risk factor.

Evaluation of early and late postoperative flow capacity of internal thoracic artery bypass by means of stress Doppler echocardiography.

OBJECTIVES: Arterial revascularization with the internal thoracic artery (ITA) has shown exceptional long-term results, even though early hypoperfusion can occur and can cause ischemia and contractile dysfunction. Therefore, it is still controversial as to whether the bypass vessel can guarantee the required demand for blood flow during the early postoperative (EPO) phase or whether this is only possible a long time after the operation. This question is important particular in the early postoperative phase to manage afterload and reduce left ventricular oxygen demand. Therefore, stress Doppler echocardiography was performed to assess EPO and late postoperative (LPO) flow capacity after minimal-invasive coronary artery bypass grafting (MIDCAB) in subjects with single vessel disease. METHODS: Doppler echocardiography was performed after MIDCAB in 15 patients (mean age 65 years+/-12 standard deviation) in the EPO (15 days) and LPO (266 days) at rest and under stress. RESULTS: The mean diastolic velocity (MDV) as a measure for the coronary perfusion in the bypass-graft was comparable (30.9+/-14.5 EPO to 30.8+/-13.9 cm/s LPO, P>0.05) for both settings (early vs. late). In both tests, the stress reactions by means of handgrip maneuver lead to comparable increases in blood flow: MDV 65.0+/-54.4% (EPO) to 62.5+/-53.7% n.s. (LPO). The flow increase in the bypass graft was just as similar [48.2+/-46.2% (EPO) to 51.1+/-41.6% n.s. (LPO)]. CONCLUSION: The stress echocardiography revealed for the first time that the ITA-graft after MIDCAB-operation is able to produce the same flow reserve through the EPO phase as well as the LPO phase. Restrictions to a maximum early flow adaptation are not justified. Thus, particularly a patient with severe comorbidities or higher age should be mobilized in the EPO phase to minimize the postoperative complications without risk of myocardial ischemia caused by impaired early blood flow through recent implanted ITA. This method for assessment of ITA blood flow allows for long-time observations and can detect disturbances in perfusion at an early stage.

Comparison of usefulness of heart-type fatty acid binding protein versus cardiac troponin T for diagnosis of acute myocardial infarction.

We aimed to assess the additive diagnostic value of measuring the serum levels of soluble human heart-type fatty acid binding protein (H-FABP) in the early diagnosis of acute myocardial infarction (AMI) in unselected patients with chest pain. A total of 97 consecutive patients with acute ischemic-type chest pain were prospectively enrolled and classified according to the American Heart Association/American College of Cardiology guidelines. The test characteristics of H-FABP and cardiac troponin T serum levels at admission revealed a greater sensitivity of H-FABP in the first 4 hours of symptoms (86% vs 42%, p <0.05). Combining H-FABP and cardiac troponin T also improved the sensitivity in the detection of AMI (97% vs 71%, p <0.05) but demonstrated a greater misclassification rate (25% vs 9%, p <0.05). The specificity of H-FABP was poor (65%, 95% confidence interval 58% to 71%). Receiver operating characteristics revealed a poor performance of H-FABP in patients with non-ST-elevation myocardial infarction. Classification tree analysis demonstrated that an H-FABP-related improvement in the early definite rule-out of AMI (reduction of false-negative rate from 11% to 3%) was at the expense of an increase in the false-positive rate to 5%. In conclusion, measurement of H-FABP, in addition to cardiac troponin T, serum levels within the first 4 hours of symptoms improves the sensitivity and negative predictive value for the detection of AMI at the cost of test accuracy and precision, especially in patients with non-ST-elevation myocardial infarction.

Screening for undiagnosed diabetes in patients with acute myocardial infarction.

BACKGROUND: Screening for undiagnosed diabetes in patients with acute myocardial infarction is recommended (ESC and EASD Task Force 2007). Glucose tolerance testing in the peri-infarct period may not be valid because of confounding, e.g. by the acute stress reaction. The aim was to evaluate undiagnosed diabetes (DM) and impaired glucose regulation (IGR) in AMI during hospital stay and 3 months after discharge. MATERIALS AND METHODS: In 96 consecutively admitted AMI patients (Heart Center Wuppertal, Germany) OGTT were performed, of whom in 62 OGTT were also carried out 3 months later. RESULTS: Before discharge 32% of the patients had newly diagnosed diabetes and 47% patients had prediabetes (IGR). Glucose tolerance was normal in 20 (21%) patients only. After 3 months, 74% with newly diagnosed DM at baseline still had disturbed glucose metabolism (58% DM, 16% IGT). No patient with normal OGTT became diabetic after 3 months. In multivariate regression, the odds of having diabetes (3 months) was about sixfold higher when having diabetes before discharge (OGTT). Admission glucose, infarction size CK(MAX), and inflammation (CRP) were not significantly related to OGTT results. CONCLUSIONS: This prospective study confirms a high prevalence of undiagnosed DM in patients with AMI. In about 60% of AMI patients, newly diagnosed DM persisted after 3 months. For the first time we could show that there is no correlation between infarction size and undiagnosed diabetes. Thus, an OGTT performed before discharge may provide a reliable measure of disturbed glucose regulation but needs to be repeated.

Atrial tachycardias following circumferential pulmonary vein ablation: observations during catheter ablation.

Circumferential pulmonary vein ablation performing linear lesions around the ostia of the pulmonary veins has been shown to be effective for the treatment of atrial fibrillation. During the follow-up period, persistent atrial tachycardia may occur as a proarrhythmic complication. Only little information is available about the underlying mechanism. In our study, atrial tachycardia following circumferential pulmonary vein ablation was identified in 13 out of 84 consecutive patients (15.5%), as a transient appearance in four and with recurrences for more than 3 months in nine patients (10.7%). Electrophysiological study and ablation was performed in eight cases, revealing common atrial flutter in two, a focal origin secondary to conduction recovery from the pulmonary vein to the left atrium in two and macro reentrant left atrial flutter in four patients. The electrophysiological characteristics demonstrated by electroanatomic activation mapping CARTO and consecutive ablation therapy with a 100% success rate are described and discussed with regard to the literature.

Prognostic significance of exercise stress echocardiography in 3329 outpatients (5-year longitudinal study).

BACKGROUND: Appraisal of the risk to which outpatients with chest pain are exposed is a major clinical problem. Up to now, there have been no reports on the prognostic significance of exercise stress echocardiography in this patient cohort. PATIENTS AND METHODS: In order to investigate the prognostic significance of exercise stress echocardiography (SE) in outpatients only, 3329 patients were monitored during a long-term follow-up regarding the occurrence of hard events (cardiac death, myocardial infarction, revascularization). The patients came to the cardiology practice complaining of chest pain. RESULTS: The sensitivity/specificity of SE for hard events was 81.1/92.8 in the first year, that of exercise ECG, 27.4/87.0. During the observation period (5.1+/-1.1 years (median 5.2, 3-7 years)), a total of 446 (13.4%) hard events occurred. In patients with positive SE findings, 262 (61.9%) hard events occurred, in patients with negative SE findings, hard events were rarer (184, 6.3%, p<0.001). In the multivariate analysis, the positive SE finding was the most unambiguous, significant independent predictor of hard events (HR 6.6, CI 5.21-8.25, p<0.001). CONCLUSIONS: In outpatients with chest pains, exercise stress echocardiography is of major prognostic significance (independent of other parameters) and its prognostic reliability is clearly superior to that of the exercise ECG. SE should always be performed in cases with symptoms requiring clarification.

Disturbed endothelial function of the internal thoracic artery in patients with coronary artery disease.

OBJECTIVES AND BACKGROUND: The internal thoracic artery is an established arterial graft for myocardial revascularization. It never had been investigated, whether there are functional differences in this vessel between patients with or without coronary artery disease. METHODS: We investigated the left internal thoracic artery of 28 patients (15 with and 13 without coronary artery disease) with a duplex-system at rest and with a handgrip exercise. RESULTS: Concerning the measured flow velocities at rest there was only a significant difference between the diastolic mean and peak velocity between the two groups, the other investigated parameters demonstrate no significant difference. The peak diastolic and the mean diastolic velocity was less in patients with coronary artery disease during the handgrip-test. The flow reserve was decreased in patients with coronary artery disease (12.6+/-24.0% vs. 32.3+/-30.9%, P < 0.05). CONCLUSIONS: We demonstrated, that patients with coronary artery disease have a higher peripheral resistance and a lower diastolic velocity of the internal thoracic artery during stress testing. This corresponds to a disturbed vasomotion and may be an early marker of arteriosclerosis.

Stress Doppler echocardiography of the internal thoracic artery--a new non-invasive approach for functional assessment after minimally invasive coronary bypass grafting.

Minimally invasive surgery for coronary revascularization using the left internal thoracic artery (ITA) has gained increasing interest. For control of graft function the established transcutaneous color-Doppler echocardiography in combination with a stress-test was performed to test the ability of this novel technique. Twenty-one patients having received a single ITA-graft were evaluated early postoperatively at rest and during isometric stress test with a handgrip exercise. Compared to the right internal thoracic artery, the mainly systolic flow is changed to a wide diastolic component when the left ITA is anastomosed to the coronary artery. The peak systolic/peak diastolic velocity ratio changed from 4.5+/-1.9 to 1.4+/-0.47 (P<0.0001). During stress reaction with the isometric handgrip maneuver the grafted ITA showed a significant increase of the mean diastolic flow (29.1+/-13.3 to 44.3+/-14.7 cm/s, P<0.0001) and total blood flow (124.8+/-55.4 ml/min to 176.6+/-71.7 ml/min), which may demonstrate an efficient bypass function. We conclude, that the noninvasive measurement of ITA-graft function with Doppler-ultrasound may be a clinically useful method to assess the functional status after minimally invasive coronary artery bypass grafting. In combination with the hand-grip test it represents a valid new technique with the potential to estimate graft patency.

[Catheter ablation of ventricular outflow tract arrhythmias using an electroanatomic mapping system]. / Katheterablation von ventrikulären Ausflusstrakt-Arrhythmien unter Einsatz eines elektroanatomischen Mapping-Systems.

BACKGROUND: In some patients with arrhythmias originating from the ventricular outflow tract, catheter ablation may be considered for curative treatment. The conventional ablation procedure may be limited particularly in cases with nonsustained arrhythmias. Only little information is available about three-dimensional electroanatomic mapping combined with the cooled radiofrequency (RF) catheter ablation technique in the treatment of such arrhythmias. PATIENTS AND METHODS: 17 symptomatic and drug-refractory patients were included into this study. Using an electroanatomic mapping system (CARTO), activation mapping was obtained in twelve patients during ventricular tachycardia (VT) or ventricular ectopic beats. In five cases with nonsustained arrhythmias pace mapping during sinus rhythm was performed. The aim was to identify the precise localization of the arrhythmia origin and to abolish its activity by cooled ablation. RESULTS: Procedure time was 117 +/- 35 min, fluoroscopy time totaled 17 +/- 13 min. Ablation was performed with a mean of 7 +/- 5 ablation pulses. In 15 patients (88%) ablation of the clinical VT was acutely successful. During a follow-up of 9 +/- 9 months, two patients had a recurrence of the clinical VT. In one of these cases a successful reablation was performed. No major complications were observed. CONCLUSION: Electroanatomic mapping combined with focal cooled ablation strategy is a safe method to treat ventricular outflow tract arrhythmias effectively.

Circumferential pulmonary vein ablation for treatment of atrial fibrillation using an irrigated-tip catheter.

In this study, a series of 52 consecutive patients with atrial fibrillation from 1 institution underwent circumferential pulmonary vein ablation using an irrigated-tip catheter. The technique was safe, and 81% of the patients maintained sinus rhythm at 6 months. However, 1/3 of them required additional antiarrhythmic drug therapy.

Angioplasty of the internal thoracic artery bypass-graft an alternative to reoperation.

BACKGROUND: This review presents an overview of interventional revascularization procedures of the internal thoracic artery after prior implantation as a coronary-artery bypass graft. METHODS: Our search was concentrated on the MEDLINE-database to identify all articles on internal thoracic artery-graft-angioplasties and reoperation after internal thoracic artery bypass grafting published between 1968 and 2000. RESULTS: Surgical revascularization and reoperation were reported in five papers including a total of 785 patients. The overall mortality of these patients was 4.2%. The presence of a patent internal thoracic artery-graft at the time of reoperation was not a risk factor for higher morbidity and mortality. Revascularization with percutaneous transluminal coronary angioplasty of the internal thoracic artery or the native left anterior descending artery via the internal thoracic artery-graft used as a conduit was performed in 327 patients. The primary success rate was 87%, the angiographically assessed rate of restenosis was 30% and the rate of complications approximately 1%. CONCLUSIONS: In spite of technical problems the percutaneous transluminal coronary angioplasty in or via internal thoracic artery-graft presents a safe and feasible option to be recognized before a potential reoperation.

Recurrent syncope in a young patient with long QT syndrome: possible relationship of atrioventricular nodal re-entrant tachycardia with neurally mediated spells?

This is a case of a 15-year-old woman with long QT syndrome (LQTS) and a history of 14 events of syncope, demonstrating that the underlying mechanism for any symptomatic episode is not necessarily based on torsades de pointes. The need for careful distinction between true ventricular tachyarrhythmia and other forms of supraventricular tachycardia in the LQTS is the subject of the article. To the knowledge of the authors, this is the first reported case of an association of LQTS with AV nodal re-entrant tachycardia.

Direct visualization of left ventricular free wall rupture by levocardiography.

Two cases of left ventricular free wall rupture and one case of combined left ventricular free wall and ventricular septal rupture are described where ventriculography played a key role in diagnosis. In all three cases of patients with acute myocardial infarction, identification and localization of the defect was made by angiography. This report illustrates the safety and feasibility of ventriculography in patients with suspected cardiac rupture.

C/T polymorphism of the intercellular adhesion molecule-1 gene (exon 6, codon 469). A risk factor for coronary heart disease and myocardial infarction.

BACKGROUND: The intercellular adhesion molecule-1 (ICAM-1) mediates the interaction of activated endothelial cells with leukocytes and plays a fundamental role in the pathogenesis of coronary atherosclerosis. ICAM-1 single-base C/T polymorphism, which determines an amino acid substitution in the ICAM-1 protein in exon 6 codon 469, has been described. Our purpose was to determine whether this C/T polymorphism influences the risk of coronary heart disease (CHD) and myocardial infarction (MI) in humans. METHODS AND RESULTS: We enrolled 349 patients with angiographically documented CHD, including a sub-group of 179 patients with acute or chronic MI. The control group consisted of 213 patients with normal left ventricular function and no documented evidence of CHD. All patients and controls were Germans genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for the ICAM-1 polymorphism. In the patients with CHD and MI the frequencies of the T genotype (TT+TC) were significantly higher than the CC genotype compared to the control subjects (P<0.001). With the additional use of multivariable logistic regression analysis for CHD (TT+TC versus CC; P=0.011, odds ratio 2.21, 95% CI 1.20-4.07), we found a significant association between CHD and MI and the TT and TC genotype of the ICAM-1 gene polymorphism. CONCLUSIONS: These results suggest that the TT and TC genotype of the ICAM-1 gene polymorphism in codon 469 is a genetic factor that may determine an individual's susceptibility for CHD and MI.