Ladislav Groch

Long distance transport for primary angioplasty vs immediate thrombolysis in acute myocardial infarction: Final results of the randomized national multicentre trial-PRAGUE-2

BACKGROUND Primary percutaneous coronary intervention (PCI) is shown to be the most effective reperfusion strategy in acute myocardial infarction. The aim of this multicentre national randomized mortality trial was to test whether the nationwide change in treatment guidelines (transportation of all patients to PCI centres) was warranted. METHODS The PRAGUE-2 study randomized 850 patients with acute ST elevation myocardial infarction presenting within <12 h to the nearest community hospital without a catheter laboratory to either thrombolysis in this hospital (TL group, n=421) or immediate transport for primary percutaneous coronary intervention (PCI group, n=429). The primary end-point was 30-day mortality. Secondary end-points were: death/reinfarction/stroke at 30 days (combined end-point) and 30-day mortality among patients treated within 0-3 h and 3-12 h after symptom onset. Maximum transport distance was 120 km. RESULTS Five complications (1.2%) occurred during the transport. Randomization-balloon time in the PCI group was 97+/-27 min, and randomization-needle time in the TL group was 12+/-10 min. Mortality at 30 days was 10.0% in the TL group compared to 6.8% mortality in the PCI group (P=0.12, intention-to-treat analysis). Mortality of 380 patients who actually underwent PCI was 6.0% vs 10.4% mortality in 424 patients who finally received TL (P<0.05). Among 299 patients randomized >3 h after the onset of symptoms, the mortality of the TL group reached 15.3% compared to 6% in the PCI group (P<0.02). Patients randomized within <3 h of symptom onset (n=551) had no difference in mortality whether treated by TL (7.4%) or transferred to PCI (7.3%). A combined end-point occurred in 15.2% of the TL group vs 8.4% of the PCI group (P<0.003). CONCLUSIONS Long distance transport from a community hospital to a tertiary PCI centre in the acute phase of AMI is safe. This strategy markedly decreases mortality in patients presenting >3 h after symptom onset. For patients presenting within <3 h of symptoms, TL results are similar results to long distance transport for PCI.

Long distance transport for primary angioplasty vs immediate thrombolysis in acute myocardial infarction

BACKGROUND Primary percutaneous coronary intervention (PCI) is shown to be the most effective reperfusion strategy in acute myocardial infarction. The aim of this multicentre national randomized mortality trial was to test whether the nationwide change in treatment guidelines (transportation of all patients to PCI centres) was warranted. METHODS The PRAGUE-2 study randomized 850 patients with acute ST elevation myocardial infarction presenting within <12 h to the nearest community hospital without a catheter laboratory to either thrombolysis in this hospital (TL group, n=421) or immediate transport for primary percutaneous coronary intervention (PCI group, n=429). The primary end-point was 30-day mortality. Secondary end-points were: death/reinfarction/stroke at 30 days (combined end-point) and 30-day mortality among patients treated within 0-3 h and 3-12 h after symptom onset. Maximum transport distance was 120 km. RESULTS Five complications (1.2%) occurred during the transport. Randomization-balloon time in the PCI group was 97+/-27 min, and randomization-needle time in the TL group was 12+/-10 min. Mortality at 30 days was 10.0% in the TL group compared to 6.8% mortality in the PCI group (P=0.12, intention-to-treat analysis). Mortality of 380 patients who actually underwent PCI was 6.0% vs 10.4% mortality in 424 patients who finally received TL (P<0.05). Among 299 patients randomized >3 h after the onset of symptoms, the mortality of the TL group reached 15.3% compared to 6% in the PCI group (P<0.02). Patients randomized within <3 h of symptom onset (n=551) had no difference in mortality whether treated by TL (7.4%) or transferred to PCI (7.3%). A combined end-point occurred in 15.2% of the TL group vs 8.4% of the PCI group (P<0.003). CONCLUSIONS Long distance transport from a community hospital to a tertiary PCI centre in the acute phase of AMI is safe. This strategy markedly decreases mortality in patients presenting >3 h after symptom onset. For patients presenting within <3 h of symptoms, TL results are similar results to long distance transport for PCI.

Prevalence of normal coronary angiography in the acute phase of suspected ST-elevation myocardial infarction: Experience from the PRAGUE studies

BACKGROUND Acute ST-elevation myocardial infarction in patients with normal coronary arteries has previously been described, but coronary angiography in these patients was performed after the acute phase of the infarction. It is possible that these patients did not have normal angiograms during the acute phase (transient coronary thrombosis or spasm were usually suspected to be the cause). Information on the prevalence of truly normal coronary angiograms during the acute phase of a suspected ST-elevation myocardial infarction is lacking. PATIENTS AND METHODS The Primary Angioplasty in patients transferred from General community hospitals to specialized PTCA Units with or without Emergency thrombolysis-1 (PRAGUE-1) and PRAGUE-2 studies enrolled 1150 patients with ST-elevation acute myocardial infarction, in whom 625 coronary angiograms were performed within 2 h of the initial electrocardiogram. A simultaneous registry included an additional 379 coronary angiograms performed during the ST-elevation phase of a suspected myocardial infarction. Thus, a total of 1004 angiograms were retrospectively analyzed. A normal coronary angiogram was defined as one with the absence of any visible angiographic signs of atherosclerosis, thrombosis or spontaneous spasm. RESULTS Normal coronary angiograms were obtained for 26 patients (2.6%). Among these, the diagnosis at discharge was a small myocardial infarction in seven patients (0.7%), acute (peri)myocarditis in five patients, dilated cardiomyopathy in four patients, hypertension with left ventricular hypertrophy in three patients, pulmonary embolism in two patients and misinterpretation of the electrocardiogram (ie, no cardiac disease) in five patients. Seven patients with small infarctions underwent angiography within 30 min to 90 min of complete relief of the signs of acute ischemia, and thus, angiograms during pain were not taken. None of the 898 patients catheterized during ongoing symptoms of ischemia had a normal coronary angiogram. Spontaneous coronary spasm as the only cause (without underlying coronary atherosclerosis) for the evolving infarction was not seen among these 898 patients. Thus, the causes of the seven small infarcts in patients with normal angiograms remain uncertain. CONCLUSIONS The observed prevalence of normal coronary angiography in patients presenting with acute chest pain and ST elevations was 2.6%. Most of these cases were misdiagnoses, not infarctions. A normal angiogram during a biochemically confirmed infarction is extremely rare (0.7%) and was not seen during the ongoing symptoms of ischemia.

Prognosis of patients with chronic coronary artery disease and severe left ventricular dysfunction. The importance of myocardial viability

The choice of optimal treatment strategy in patients with coronary artery disease (CAD) and severe left ventricular (LV) dysfunction is often difficult. The aim of this study was to compare long‐term results of patients with chronic CAD, severe heart failure and a defined scope of myocardial viability treated with coronary revascularization, heart transplantation, or kept on medical therapy.

Low Incidence of Procedure-Related Major Adverse Cardiac Events After Alcohol Septal Ablation for Symptomatic Hypertrophic Obstructive Cardiomyopathy

BACKGROUND Alcohol septal ablation (ASA) is a catheter-based intervention that has been used as an alternative to surgical myectomy in highly symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM). However, clinically relevant complications can result, including death and complete heart block (CHB) associated with syncope or resuscitation. This study was designed to evaluate the incidence of major ASA-related adverse cardiac events. METHODS This international multicentre retrospective study included 421 patients in 8 European centres who were treated using ASA from April 1998 to January 2011. Clinical and echocardiographic follow-up (3-6 months) was completed in 394 patients (94%). RESULTS ASA led to a significant reduction in symptoms and outflow gradients, with 0.7% mortality. A total of 70 patients (17%) experienced mostly transient CHB during and after the procedure; in 30% of them, CHB occurred or recurred later than 24 hours after ASA. Ninety-seven percent of CHB occurred up to the fifth day after ASA. Permanent pacemakers for CHB were implanted in 35 patients (8%). Multivariate analysis identified intraprocedural bundle branch block and age as independent predictors of CHB. CONCLUSIONS The results of the multicentre study demonstrate that ASA appears safe and efficacious, with low early mortality. The most frequent major complication after ASA was CHB (17%), which occurred late or was recurrent in almost one-third of these patients; 8% of patients required permanent pacemaker implantation. Independent predictors of CHB development were intraprocedural bundle branch block and age. Difficulty in predicting CHB should lead to close postprocedural monitoring and hospital stays lasting at least 5 days.

Intracoronary Delivery of Bone Marrow Cells to the Acutely Infarcted Myocardium

Objectives: Intracoronary cell transplantation during catheter balloon inflations may be associated with adverse events. We studied the effectiveness of an alternative transplantation technique – intracoronary cell infusion. Methods: Fourteen pigs, which had survived acute myocardial infarction, were randomized into 2 treatment groups and 2 controls. Three days after infarction, 12 pigs underwent allogeneic intracoronary mononuclear bone marrow cell transplantation using either the standard technique (short-term cell injections during repeat balloon inflations, technique A, n = 6) or continuous intracoronary cell infusion without balloon inflations (technique B, n = 6). Implanted cells were stained with fluorescent dye. After transplantation, the pigs were euthanized and myocardial samples were analyzed by fluorescent microscopy. Results: The mean numbers of fluorescently labeled bone marrow cells in the infarction border zone, in the infarction mid-area and in the center of myocardial infarction were 84, 72 and 55 using technique A, and 29, 57 and 46 using technique B, respectively. The mean cell retention in the infarction border zone of 84 cells for technique A and 29 cells for technique B differed significantly (p = 0.034, two-tailed t test). Conclusion: The continuous intracoronary cell infusion technique is a less efficient cell delivery technique as compared with the standard technique using repeat intracoronary balloon inflations.

Variability of changes in Doppler transmitral filling pattern during stress echocardiography in patients with stable angina pectoris

Stress electrocardiography and echocardiography using atrial pacing together with the right-sided heart catheterization were performed in 21 patients with stable angina pectoris. Peak velocity of transmitral flow in early diastole (E) and in atrial contraction (A), deceleration time of early filling, and pulmonary artery wedge pressure were measured simultaneously at rest and immediately after each pacing frequency. Patients were divided according to their stress pulmonary artery wedge pressure changes into Group A (14 patients with an increase in pulmonary artery wedge pressure > or = 3 mmHg during stress) and into Group B (6 patients with a change in pulmonary artery wedge pressure < or = 2 mmHg during stress). One patient, T.L., with an increase in pulmonary artery wedge pressure > or = 5 mmHg after each pacing frequency was evaluated separately. In Group A patients, the non-linear course of the E/A ratio changes (from 0.78 +/- 0.06 to 0.66 +/- 0.05, P < 0.01; to 0.72 +/- 0.05, P = NS; and to 0.93 +/- 0.06, P < 0.01) and deceleration time changes (from 188.9 +/- 7.2 ms to 195.3 +/- 8.9 ms, P = NS; to 188.8 +/- 9.9 ms, P = NS; and to 154.2 +/- 6.7 ms, P < 0.01) was seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic importance of the quantification of myocardial viability in revascularized patients with coronary artery disease and moderate-to-severe left ventricular dysfunction.

The aim of this study was to assess the prognostic value of the amount of dysfunctional but viable myocardium in revascularized patients with coronary artery disease and left ventricular dysfunction. To quantify the amount of dysfunctional but viable myocardium, low-dose dobutamine echocardiography was performed. The wall motion was scored using a 16-segment model. The dysfunctional segments were defined as viable if they exhibited functional improvement of at least 1 grade with any dose of dobutamine, or only worsening with dobutamine infusion. Two hundred and twenty patients were revascularized and followed-up for a mean period of 33+/-23 months (range, 0-86) for cardiac-related death and hospitalization for heart failure. Standard follow-up echocardiography was performed 3-6 months after revascularization. Receiver operating characteristic curve analysis identified six dysfunctional but viable segments as the optimal cutoff value for discriminating patients with and without risk of cardiac events. Thirty-eight patients exhibited a large amount of dysfunctional but viable myocardium (>or=6 segments, group A), 103 patients had a small amount of dysfunctional but viable myocardium (2-5 segments, group B), and 79 patients were found to have dysfunctional myocardium irreversibly damaged (group C). Similar baseline left ventricular ejection fractions of 36+/-4, 34+/-5, 35+/-5% in groups A, B, and C increased to 46+/-6% (P<0.01 versus baseline and versus groups B and C), to 39+/-5% (P<0.01 versus baseline and group C), and to 36+/-7% (P<0.01 versus baseline), respectively, after revascularization. The greatest functional improvement after revascularization in group A patients was accompanied by a lower frequency of cardiac events during follow-up (1 vs. 27 in group B, P<0.01, and versus 18 in group C, P<0.01) and by a better cardiac event-free survival according to Kaplan-Meier survival analysis (P<0.01 versus groups B and C, respectively). In conclusion, in revascularized patients with coronary artery disease and moderate-to-severe left ventricular dysfunction, the presence of >or=6 dysfunctional but viable segments identifies patients with the best prognosis.

Patients with chronic three-vessel disease in a 15-year follow-up study: genetic and non-genetic predictors of survival.

AbstractGenetic and non-genetic predictors of 15-year survival in patients with chronic three-vessel disease (3VD) were investigated.Coronary angiography was performed on 810 subjects with symptoms of stable ischemic heart disease in 1998. The patients with 3VD were genotyped for 23 candidate polymorphisms covering the PPAR-RXR pathway, matrix metalloproteinase-2, renin–angiotensin–aldosterone system, endothelin-1, cytokine genes, MTHFR and APO E variants. Fifteen-year survival data were obtained from the national insurance registry. All data were available in the case of 150 patients with 3VD. Statistical analysis used stepwise Cox regression with dominant, recessive, or additive mode of genetic expression. Involved variables included age, sex, BMI, blood pressure, diabetes, ejection fraction, left main stenosis, previously diagnosed coronary stenosis, myocardial infarction in personal history, and coronary bypass along with polymorphisms pre-selected by log-rank tests.Out of the 23 polymorphisms, four were included in the model construction. SNP in the IL-6 gene rs1800795 (−174 G/C) has been found to be a significant predictor of survival. This SNP was in a linkage disequilibrium with rs1800797 (−597 G/A) in the same gene (D′ = 1.0), which was also found to constitute a significant predictor of survival when rs1800795 was not included in the model construction. Age, increased BMI, diabetes, low EF, and left main stenosis were also significant predictors in all models.Age, increased BMI, diabetes, low ejection fraction, left main stenosis, and genetic variation in the IL-6 promoter were established as significant independent risk factors for the survival of patients with three-vessel disease.

Apolipoprotein E polymorphism is associated with both number of diseased vessels and extent of coronary artery disease in Czech patients with CAD

AIMS The impact of ApoE polymorphism on angiographic parameters was assessed in patients referred for coronary angiography. METHODS Elective coronary angiography was performed in 671 subjects (525 men, 146 women, mean age 60 ± 10 years) with symptoms of ischemic heart disease. The patients were divided into: no CAD group (smooth coronary vessels, n=83), one-vessel (n=155), two-vessel (n=170) and three-vessel disease (n=196). Patients with stenoses 0-50% were excluded. Within patients with CAD, we evaluated overall extent of CAD measured by the number of stenotic segments according to AHA (1 segment vs. 2-3 vs. ≥4), and the severity of the most serious stenosis (in percent). ApoE genotype was determined using real-time PCR. RESULTS The frequency of ε2/ε3 genotype (n=56) was lower in the three-vessel disease group compared to one-vessel disease (OR=0.25, P=0.0019), two-vessel disease (OR=0.31, P=0.0114) or no CAD group (OR=0.24, P=0.0057). Frequency of ε2/ε3 decreased with the number of affected segments (1 vs. ≥4: OR=0.35, P=0.0143). The ε3/ε4+ε4/ε4 genotypes (n=123) were more frequent in CAD patients altogether compared with no CAD group (OR=2.30, P=0.019), while no impact of the ε4 allele on angiographic parameters within the CAD patients was detected. In ε2/ε3 carriers with CAD, lower LDL-cholesterol, total cholesterol and lower use of lipid-lowering drugs were observed. CONCLUSIONS The results show predominantly focal form of CAD in patients with ε2/ε3 genotype. Lower LDL-cholesterol and total cholesterol may play the key role, although other contributing factors are discussed.