A Dutch MYH7 founder mutation, p.(Asn1918Lys), is associated with early onset cardiomyopathy and congenital heart defects.

BACKGROUND: Mutations in the myosin heavy chain 7 (MYH7) gene commonly cause cardiomyopathy but are less frequently associated with congenital heart defects. METHODS: In this study, we describe a mutation in the MYH7 gene, c. 5754C > G; p. (Asn1918Lys), present in 15 probands and 65 family members. RESULTS: Of the 80 carriers (age range 0-88 years), 46 (57.5%) had cardiomyopathy (mainly dilated cardiomyopathy (DCM)) and seven (8.8%) had a congenital heart defect. Childhood onset of cardiomyopathy was present in almost 10% of carriers. However, in only a slight majority (53.7%) was the left ventricular ejection fraction reduced and almost no arrhythmias or conduction disorders were noted. Moreover, only one carrier required heart transplantation and nine (11.3%) an implantable cardioverter defibrillator. In addition, the standardised mortality ratio for MYH7 carriers was not significantly increased. Whole exome sequencing in several cases with paediatric onset of DCM and one with isolated congenital heart defects did not reveal additional known disease-causing variants. Haplotype analysis suggests that the MYH7 variant is a founder mutation, and is therefore the first Dutch founder mutation identified in the MYH7 gene. The mutation appears to have originated in the western region of the province of South Holland between 500 and 900 years ago. CONCLUSION: Clinically, the p. (Asn1918Lys) mutation is associated with congenital heart defects and/or cardiomyopathy at young age but with a relatively benign course.

A rare stress cardiomyopathy in a patient with Guillain-Barré syndrome.

We report on a 39-year-old woman who was intubated because of progressive respiratory failure due to muscle weakness and mucous plugging because of Guillain- Barré syndrome. Shortly after uncomplicated intubation she developed hypotension and a profound tachycardia. The electrocardiogram showed sinus tachycardia with nonspecific ST-T segment changes. Echocardiography showed akinesia of the apex, septum and inferior left ventricular wall with an estimated left ventricular ejection fraction of 10%. It was concluded that the patient was suffering from takotsubo cardiomyopathy. Following treatment, she experienced a complete recovery. Takotsubo cardiomyopathy is a rare complication in Guillain-Barré syndrome; eight other cases have been reported in the literature.

A prospective validation of the HEART score for chest pain patients at the emergency department.

BACKGROUND: The focus of the diagnostic process in chest pain patients at the emergency department is to identify both low and high risk patients for an acute coronary syndrome (ACS). The HEART score was designed to facilitate this process. This study is a prospective validation of the HEART score. METHODS: A total of 2440 unselected patients presented with chest pain at the cardiac emergency department of ten participating hospitals in The Netherlands. The HEART score was assessed as soon as the first lab results and ECG were obtained. Primary endpoint was the occurrence of major adverse cardiac events (MACE) within 6 weeks. Secondary endpoints were (i) the occurrence of AMI and death, (ii) ACS and (iii) the performance of a coronary angiogram. The performance of the HEART score was compared with the TIMI and GRACE scores. RESULTS: Low HEART scores (values 0-3) were calculated in 36.4% of the patients. MACE occurred in 1.7%. In patients with HEART scores 4-6, MACE was diagnosed in 16.6%. In patients with high HEART scores (values 7-10), MACE occurred in 50.1%. The c-statistic of the HEART score (0.83) is significantly higher than the c-statistic of TIMI (0.75)and GRACE (0.70) respectively (p<0.0001). CONCLUSION: The HEART score provides the clinician with a quick and reliable predictor of outcome, without computer-required calculating. Low HEART scores (0-3), exclude short-term MACE with >98% certainty. In these patients one might consider reserved policies. In patients with high HEART scores (7-10) the high risk of MACE may indicate more aggressive policies.

Magnetic resonance imaging, pacemakers and implantable cardioverter-defibrillators: current situation and clinical perspective.

New developments and expanding indications have resulted in a significant increase in the number of patients with pacemakers and internal cardioverterdefibrillators (ICDs). Because of its unique capabilities, magnetic resonance imaging (MRI) has become one of the most important imaging modalities for evaluation of the central nervous system, tumours, musculoskeletal disorders and some cardiovascular diseases. As a consequence of these developments, an increasing number of patients with implanted devices meet the standard indications for MRI examination. Due to the presence of potential life-threatening risks and interactions, however, pacemakers and ICDs are currently not approved by the Food and Drug Administration (FDA) for use in an MRI scanner. Despite these limitations and restrictions, a limited but still growing number of studies reporting on the effects and safety issues of MRI and implanted devices have been published. Because physicians will be increasingly confronted with the issue of MRI in patients with implanted devices, this overview is given. The effects of MRI on an implanted pacemaker and/or ICDs and vice versa are described and, based on the current literature, a strategy for safe performance of MRI in these patients is proposed. (Neth Heart J 2010;18:31-7.).

[Partial resistance to acenocoumarol and phenprocoumon caused by enzyme polymorphism]. / Partiële acenocoumarol- en fenprocoumonresistentie door enzympolymorfisme.

A 78-year-old man was treated with coumarin derivatives following myocardial infarction. The international normalised ratio was not increased by using standard loading doses and dose adjustments for acenocoumarol and phenprocoumon. The desired level of anticoagulation was achieved with a high dosage of phenprocoumon (18-21 mg daily). This dose was associated with a phenprocoumon serum concentration that was ten times higher than the normal therapeutic concentration. The serum concentration of vitamin K1 was low. After exclusion of alternative causes, we concluded that the exceptionally high dose of phenprocoumon needed was due to partial resistance to coumarin derivatives. Partial resistance is related to a polymorphism of the gene coding for the enzyme vitamin K epoxide reductase. The patient was successfully treated with chronic high-dose phenprocoumon. Resistance to coumarin derivatives caused by a congenital polymorphism in the vitamin K reductase gene is a rare phenomenon. Resistance is seldom absolute. The desired anticoagulation effect can be achieved with doses that are 10-20 times higher than standard doses. Phenprocoumon is advantageous in this situation because it requires fewer tablets than acenocoumarol. Determination of serum concentrations of acenocoumarol and phenprocoumon can be used to exclude other causes of treatment resistance.

Mural aortic thrombus and peripheral embolisation in a patient with hyperhomocysteinaemia.

A mobile thrombus of the descending thoracic aorta in young people is extremely uncommon. We describe a 38-year-old woman with a mural thrombus in the proximal aorta complicated by peripheral embolisation, due to hyperhomocysteinaemia.

[Shoshin beriberi provoked by the inhalation of salbutamol]. / Sjosjin-beriberi na inhalatie van salbutamol.

A 45-year-old male alcoholic with a deficient diet was given salbutamol for exertion-related dyspnoea. After inhalation, he presented with a severe dyspnoea, acrocyanosis, anuria and low blood pressure as well as a respiratory compensated lactate acidosis. Shoshin beriberi was suspected on clinical grounds. The low level of thiamine and the prompt recovery after thiamine repletion confirmed this diagnosis. Shoshin beriberi is an acute, cardiac form of beriberi, which can rapidly result in death due to cardiogenic shock and lactate acidosis. Adrenergic agents can cause a hyperdynamic circulation and thus aggravate the effects of a thiamine deficiency.

Smoking cessation reduces mortality after coronary artery bypass surgery: a 20-year follow-up study.

OBJECTIVES: The goal of this study was to determine the influence of smoking cessation on mortality after coronary artery bypass graft surgery (CABG), which has still not been established clearly. BACKGROUND: Cigarette smoking is one of the known major risk factors of coronary artery disease. METHODS: One thousand and forty-one patients underwent CABG between 1971 and 1980. The preoperative and postoperative smoking habits of 985 patients (95%) could be retrieved and were analyzed in a multivariate Cox analysis. RESULTS: The median follow-up was 20 years (range 13 to 26 years). Smoking status before surgery did not entail an increased risk of mortality: patients who had smoked before surgery and those who had not smoked in the year before surgery had a similar probability of survival. However, smoking cessation after surgery was an important independent predictor of a lower risk of death and coronary reintervention during the 20-year follow-up when compared with patients who continued smoking. In analyses adjusted for baseline characteristics, the persistent smokers had a greater relative risk (RR) of death from all causes (RR 1.68 [95% confidence interval 1.33 to 2.13]) and cardiac death (RR 1.75 [1.30 to 2.37]) as compared with patients who stopped smoking for at least one year after surgery. The estimated benefit of survival for the quitters increased from 3% at five years to 14% at 15 years. The quitters were less likely to undergo repeat CABG or a percutaneous coronary angioplasty procedure (RR 1.41 [1.02 to 1.94]). CONCLUSIONS: Patients who continued to smoke after CABG had a greater risk of death than patients who stopped smoking. They also underwent repeat revascularization procedures more frequently. Cessation of smoking is therefore strongly recommended after CABG. Clinicians are encouraged to start or to continue smoking-cessation programs in order to help smokers to quit smoking, especially after CABG.

Mortality and repeat interventions up until 20 years after aorto-coronary bypass surgery with saphenous vein grafts. A follow-up study of 1041 patients.

AIMS: To determine very long-term survival and incidence of recurrent interventions following aorto-coronary bypass surgery using venous grafts. METHODS AND RESULTS: A group of 1041 consecutive patients operated upon between 1971 and 1980 were followed for a median of 19 years (range 13-26). Peri-operative mortality was 1.2%. Survival probability at 5, 10, 15, and 20 years was 92%, 77%, 57%, and 40%, respectively. After 5 or more years following operation the mortality was higher than in the matched Dutch population. Age, extent of coronary artery disease, and ejection fraction are independent predictors of mortality. Of the 593 deceased patients at least 63% died of a probable cardiac cause, while cardiovascular mortality is 40% in the general Dutch population. Repeat revascularization procedures (aorto-coronary bypass surgery or percutaneous transluminal coronary angioplasty) were performed in 343 patients (33%), with an increasing incidence after 7 years. CONCLUSION: Aorto-coronary bypass surgery using vein grafts is safe and has a reasonable long-term prognosis for survival, although less than a matched population. After approximately 7 years both mortality and the need for repeated revascularizations increased. Since a majority of patients died of a cardiac cause and a substantial number of patients required repeated revascularization, aorto-coronary bypass surgery is a palliative treatment of a progressive disease.

Performance of an automated real-time ST-segment analysis program to detect coronary occlusion and reperfusion.

Continuously updated ST-segment recovery analysis has been shown to accurately predict infarct-related artery patency. Salient principles were converted into algorithms and incorporated into a portable ST monitor for optimal application. This study tested the automated program's ability to detect occlusion and reperfusion during balloon angioplasty. ST-segment recordings during 78 balloon occlusions in 31 patients were analyzed. The program requires at least one electrocardiogram with ST elevation of 200 microV or greater in the recording, caused by the current occlusion or by a previous occlusion, before it will yield a patency prediction. All 35 inflations causing peak ST elevation of 200 microV or more were indeed detected. All five inflations causing less than 200 microV ST elevation preceded by an inflation causing 200 microV or higher ST elevation were also detected. Occlusion was detected a median of 40 seconds after inflation, and reperfusion a median of 17 seconds after deflation. Peak ST elevation greater than 200 microV occurred in 19 of 26 left anterior descending artery inflations (73%), 1 of 22 left circumflex artery LCX inflations (5%), and 15 of 30 right coronary artery inflations (50%). Five different leads identified peak ST elevation through 12-lead surveillance. In this model of coronary occlusion during angioplasty balloon inflation, the automated patency assessment program appears to detect coronary angioplasty balloon occlusion and reperfusion within seconds in all occlusions causing a peak ST elevation of 200 microV or greater. Testing this automated patency assessment program as a noninvasive triage tool in myocardial infarction patients seems warranted.

Non-invasive prediction of reperfusion and coronary artery patency by continuous ST segment monitoring in the GUSTO-I trial.

In the GUSTO-I ECG ischaemia monitoring substudy, 1067 patients underwent continuous ST segment monitoring, using vector-derived 12-lead (406 patients), 12-lead (373 patients) and 3-lead Holter (288 patients) ECG recording systems. Simultaneous angiograms at 90 or 180 min following thrombolytic therapy were performed as a part of the prospective study in 302 patients. Infarct vessel patency was established as TIMI perfusion grades 2 or 3 and occlusion as TIMI perfusion grades 0 or 1. Coronary artery patency was predicted from ST trends up to the time of angiography. Predictive values at 90 and 180 min after the start of thrombolysis were 70% and 82% for patency and 58% and 64% for occlusion, respectively. In retrospect, accuracy appeared greatest (79-100%) in patients with extensive ST segment elevation (> or = 400 microV), if both speed of ST recovery and extent of ST segment elevation were taken into account. Although the three recording systems differed considerably in signal processing, no significant difference in accuracy was demonstrated among these systems. We conclude that continuous ECG monitoring may help select high risk patients without apparent reperfusion who may benefit from additional reperfusion therapy. As ST recovery may occur early after the start of thrombolytics and accuracy of the test is related to peak ST levels, the use of on-line ECG monitoring devices on emergency wards and cardiac care units is recommended.

The impact of autoperfusion on quantitative electrocardiographic parameters of ischemia severity, extent, and "burden" during salvage of elective coronary angioplasty.

Long angioplasty inflations have been reported using an autoperfusion system that delivers oxygenated blood distal to the balloon segment. The safety and efficacy of this system has been demonstrated in anatomically selected patients. The clinical use, however, is frequently to stabilize intimal dissection in unselected patients. We reviewed 12-lead continuous electrocardiographic (ECG) recordings in 40 patients in whom prolonged salvage with autoperfusion was attempted. Sub-optimal results were stabilized in 36 of 40, while 4 patients had urgent bypass. The presence of ischemia, as > or = 100 uV ST elevation over the 12 lead ECG, and the total ST deviation over all leads over the entire inflation period (total ischemic "burden") were compared within each patient between the longest standard balloon and autoperfusion inflations. Median duration of inflation was 3.03 min. with balloon vs. 15.6 min. with autoperfusion (p < 0.00002). Of the 40 patients, 35 (87%) had ECG ischemia with balloon vs. 18 (45%) with autoperfusion (p < .00002). Median severity of peak ST deviation was 321 uV with balloon vs. 132 uV with autoperfusion (p = 0.0001). Median extent of ST elevation was 3 leads with balloon vs. 0 leads with autoperfusion (p = 0.0001). Median total ischemic burden was similar with balloon (1173 uVmin) and autoperfusion (1083 uVmin, NS) despite the fivefold longer inflation duration with autoperfusion. Thus, in patients selected by clinical necessity rather than optimal anatomy, severity and extent of ST elevation were significantly reduced, although not entirely eliminated, by autoperfusion.

Comparison of continuous ST-segment recovery analysis with methods using static electrocardiograms for noninvasive patency assessment during acute myocardial infarction. Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) 7 Study Group.

Continuous ST-segment recovery analysis and 5 static methods using ST-segment comparison between a pre- and post-treatment electrocardiogram were compared for their ability to predict infarct-related artery patency in 82 patients with acute myocardial infarction who underwent angiography a median of 124 minutes after onset of thrombolytic treatment. Accuracy at the moment of angiography was 85% (95% confidence interval [CI] 77% to 93%) for the continuous method, and 68% (CI 57% to 78%), 78% (CI 69% to 87%), 83% (CI 74% to 91%), 82% (CI 73% to 90%), and 80% (CI 71% to 89%) for the static methods. At the moment of angiography the most accurate static method and the continuous method agreed in patency assessment in 90% of the patients (CI 84% to 97%). Agreement was reduced to 83% (CI 75% to 91%) of patients when a patency assessment was performed earlier at 90 minutes after treatment onset, and was only 77% (CI 68% to 86%), at 60 minutes. Early disagreement was mainly seen when the continuous ST recording showed ST recovery from a delayed peak ST elevation after the pretreatment static electrocardiogram or when dynamic ST changes suggesting cyclic reperfusion occurred. Continuous ST-segment recovery analysis appears to be as accurate as the most accurate static methods. Continuously updated reference points appear to give important additional information when ST recovery follows a delayed peak ST elevation or when re-elevation occurs, suggesting cyclic flow changes. Such findings appear to affect about half of patients with acute myocardial infarction treated with intravenous thrombolysis, particularly early after administration of therapy.

ST-segment recovery as an endpoint in acute myocardial infarction trials. Past, present, and future.

Traditional, comparative acute myocardial infarction trials have used morbidity and mortality as endpoints, requiring large study populations. Left ventricular function and angiographic infarct-related artery patency have, therefore, been used as alternative endpoints. These assessments are costly, risk-laden, and put a large demand on resources not available in every hospital. This has led to an increased interest in noninvasive endpoints for comparative trials. This study describes the history and possibilities of ST-segment recovery analysis as an endpoint in acute myocardial infarction trials.

Continuously updated 12-lead ST-segment recovery analysis for myocardial infarct artery patency assessment and its correlation with multiple simultaneous early angiographic observations.

Early angiography may not adequately subgroup patients with myocardial infarction if cyclic changes in coronary flow occur frequently. From a pilot experience using a new 12-lead ST-segment monitor, a continuously updated, self-referenced ST-recovery analysis method was developed to quantify both instantaneous recovery, as a noninvasive marker of patency, and cumulative ST recovery over time, as a marker of the speed, stability and duration of reperfusion. In 22 patients with acute infarction in whom 44 observations of unique angiographic patency were noted within 6 hours of presentation, serial patency assessments simultaneous with all angiographic observations predicted coronary occlusion with 90% sensitivity and 92% specificity. Of the 22 patients, 11 (50%) had multiple ST trend transitions suggesting cyclic changes in coronary flow before catheterization. Speed, stability and duration of ST-segment recovery were defined by the time to first 50% ST recovery, total number of ST-trend transitions and patent physiology index (percentage of monitoring period showing ST recovery), respectively. Subgrouped angiographically, the median (interquartile range) for cumulative ST parameters with patent (n = 8) versus occluded (n = 14) arteries were, respectively--time to 50% recovery, 1.57 (1.16, 1.70) versus 0.17 (-0.47, 0.32) hours; number of reelevation/recovery events, 1.5 (1, 3) versus 3 (1, 3); and patent physiology index, 52 (47, 59) versus 50 (5, 73). Thus, continuous ST-segment recovery analysis appears to predict simultaneous angiographic patency over serial assessments, whereas cumulative parameters appear to contain independent information, probably because of patency changes before or after angiography.

Evolution of an automated ST-segment analysis program for dynamic real-time, noninvasive detection of coronary occlusion and reperfusion.

Patients in whom early and stable reperfusion through the infarct artery fails after thrombolytic treatment might benefit from further revascularization therapy. A reliable noninvasive technique able to detect both reperfusion and reocclusion would be useful to test this hypothesis. However, no such technique presently exists. ST-segment recovery analysis using continuous digital 12-lead ST monitoring has been shown to be an accurate predictor of infarct artery patency in real time. This method was dependent on a trained clinician's analysis of the recordings on a personal computer. For optimal bedside application, salient principles of this ST-segment recovery analysis were converted into algorithms and built into the ST monitor software. The essentials of these algorithms are described in this report.

[11-year survival following aortocoronary bypass surgery]. / Overleving 11 jaar na een aorto-coronaire bypass-operatie.

To evaluate longterm survival after a first aortocoronary bypass operation we followed up all such patients with operations between July 1971 and June 1980. Included were 1041 patients, mean follow-up time was 11 years (8.5-17.4). Data were complete in 98%. The perioperative mortality equalled 1.2%, survival probability at 5 and 10 years was 92% and 77%, respectively. The yearly mortality rate increased from the fifth year onward up to 5% in the tenth. Of the deceased patients 72% had a cardiac cause of death. Extent of vascular involvement, quality of left ventricular function and age at operation had an important influence on survival probability. The aortocoronary bypass operation is a safe procedure, with a good prognosis for survival, but does not prevent cardiac death in the future.