Mode of delivery and peripartum outcome in women with heart disease according to the ESC guidelines: an Italian multicenter study.

INTRODUCTION: The European Society of Cardiology (ESC) guidelines (GL) provide indications on the mode of delivery in women with heart disease. However available data suggests that the rate of Cesarean Delivery (CD) is high and widely variable among such patients. In this study, we aimed to investigate the degree of adherence to the ESC recommendations among women delivering in four tertiary maternity services in Italy and how this affects the maternal and neonatal outcomes. MATERIAL AND METHODS: Retrospective multicenter cohort study including pregnant women with heart disease who gave birth between January 2014 and July 2020. Composite adverse maternal outcome (CAM) was defined by the occurrence of one or more of the following: major postpartum hemorrhage, thrombo-embolic or ischemic event, de novo arrhythmia, heart failure, endocarditis, aortic dissection, need for re-surgery, sepsis, maternal death. Composite Adverse Neonatal outcome (CAN) was defined as cord arterial pH <7.00, APGAR <7 at 5 min, admission to the intensive care unit, and neonatal death. We compared the incidence of CAM and CAN between the cases with planned delivery in accordance (group "ESC consistent") or in disagreement (group "ESC not consistent") with the ESC GL. RESULTS: Overall, 175 women and 181 liveborn were included. A higher frequency of CAN was found when delivery was not planned accordingly to the ESC guidelines [("ESC consistent" 9/124 (7.2%) vs "ESC not consistent" 13/57 (22.8%) p = 0.002 OR 3.74 (CI 95% 1.49-9.74) , while the occurrence of CAM was comparable between the two groups. At logistic regression analysis, the gestational age at delivery was the only parameter independently associated with the occurrence of CAN (p = 0.006). CONCLUSION: Among pregnant women with heart disease, deviating from the ESC guidelines scheduling cesarean delivery does not seem to improve maternal outcomes and it is associated with worse perinatal outcomes, mainly due to lower gestational age at birth.

Genetic predisposition to atorvastatin-induced myopathy: a case report.

WHAT IS KNOWN AND OBJECTIVE: The major clinical complication of statins is a variety of muscle complaints ranging from myalgia to rhabdomyolysis. There is growing evidence that carriers of genetic polymorphisms in the enzymes and transporters implicated in statin disposition, particularly the SLCO1B1 gene, are at increased risk of myotoxicity. Our objective is to report on two cases of statin-induced myopathy occurring in a family with two patients who are carriers of the loss of function SLCO1B1 genetic variant and to briefly review the related literature. CASE SUMMARY: Patient 1, a 48-year-old man with history of coronary artery disease, experienced rapidly evolving muscle pain and weakness of the extremities during treatment with atorvastatin 40 mg. Patient 2, a 65-year-old man, father of patient 1, had symptoms similar to those of his son after 2 weeks' treatment with the same statin. Atorvastatin was stopped in both cases, and symptoms resolved. On the basis of family relationship between the two patients, it was possible to hypothesize a genetic basis for the myopathy. Genotyping showed the patients to be carriers of the rs4363657 polymorphism of SLCO1B1 gene. WHAT IS NEW AND CONCLUSION: The two cases reported here and the brief literature review emphasize the impact of genetic factors on the risk of myopathy with statins. Although genotyping all patients before initiating therapy is not recommended at present, pharmacogenetic testing may be useful for new patients who have a family history of statin-induced myopathy.

Long-term mortality in patients unsuitable for surgical revascularization undergoing elective left main coronary artery angioplasty.

AIM: Elective percutaneous coronary intervention (PCI) of left main coronary artery disease remains an important challenge in interventional cardiology. Nonetheless, this procedure is useful for patients with significant left main stenosis who are candidates for revascularization but unsuitable for coronary artery bypass graft. In this study the Authors sought to evaluate the safety and long-term mortality of PCI of left main coronary artery disease. Secondary endpoints were to analyse long-term mortality in various categories (patients<75 years vs patients<75 years, males vs females, drug eluting stents [DES] vs bare metal stents [BMS]). METHODS: Between January 2003 and December 2006, 131 patients who consecutively under-went PCI on left main stem were reviewed. The mean follow-up time was 14.0+/-10.8 months. Survival curves were plotted with the Kaplan-Meier method and compared with the Log-rank test. RESULTS: The Kaplan-Meier curves did not show statistically significant differences in terms of all-cause mortality at follow-up between protected and unprotected left main coronary disease (12% vs 14% respectively, P=0.67). In the protected left main group, there was a significantly higher use of DES compared with unprotected left main group (59% vs 43%, P=0.02). CONCLUSION: The data show that PCI for left main coronary disease is feasible, safe and with an acceptable long-term mortality rate in patients at high-surgical risk unsuitable for surgical revascularization.

Prothrombotic genetic risk factors in young survivors of myocardial infarction.

It has long been thought that an individual thrombotic tendency increases the risk of myocardial infarction, especially in young adults. Several "prothrombotic" genetic factors that may influence the individual thrombotic risk have been identified. To investigate the association between the risk of myocardial infarction at a young age and genetic factors thought to be associated with an increased tendency to thrombosis (the polymorphisms 4G/5G of the PAI-1 gene, PIA1/PIA2 of the platelet glycoprotein IIIa, C3550T of the platelet glycoprotein Ib gene, G10976A of the factor VII gene, C677T of the methylenetetrahydrofolate reductase gene, G1691A of the factor V gene, and G20210A of the prothrombin gene), we performed a case-control study evaluating 200 survivors (185 men, 15 women) of myocardial infarction who had experienced the event before the age of 45 years and 200 healthy subjects with a negative exercise test, individually matched for sex, age, and geographic origin with the cases. The presence of the PIA2 polymorphic allele was the only prothrombotic genetic factor associated with the risk of myocardial infarction at a young age. The odds ratio for carriers of the PIA2 allele compared with those of the PIA1 allele was 1.84 (95% confidence intervals (CI) 1.12 to 3.03). There was a significant interaction between the presence of the PIA2 allele and smoking: with their simultaneous presence, 46% (95% confidence intervals 11% to 81%) of premature myocardial infarctions were attributable to the interaction between the two factors. In conclusion, carrying the PIA2 polymorphic allele of platelet glycoprotein IIIa was the only genetic prothrombotic factor associated with the risk of developing myocardial infarction at a young age. The clinical expression of this genetic predisposition seems to be enhanced by smoking.

Effect of transdermal nitroglycerin or N-acetylcysteine, or both, in the long-term treatment of unstable angina pectoris.

OBJECTIVES: This study was designed to evaluate whether the addition of transdermal nitroglycerin or oral N-acetylcysteine, or both, to conventional medical therapy improves the natural history of unstable angina pectoris. BACKGROUND: Transdermal nitroglycerin is widely used to treat angina pectoris, but the development of tolerance is a major problem that may reduce its clinical efficacy. It has been suggested that the addition of N-acetylcysteine to nitroglycerin reverses the development of tolerance, potentiates the hemodynamic response to nitroglycerin and may improve in-hospital prognosis in unstable angina. METHODS: We assessed the efficacy of adding transdermal nitroglycerin or oral N-acetylcysteine, or both, to conventional medical therapy in a randomized, double-blind, placebo-controlled trial involving 200 patients with unstable angina who were followed up for 4 months. RESULTS: Outcome events--death, myocardial infarction or refractory angina requiring revascularization--occurred in 31% of patients receiving nitroglycerin, 42% of those receiving N-acetylcysteine, 13% of those receiving nitroglycerin plus N-acetylcysteine and 39% of those receiving placebo (p = 0.0052). Kaplan-Meier curves showed a higher probability (p < 0.01) of no failure of medical treatment in the group receiving both nitroglycerin and N-acetylcysteine than in those receiving placebo, N-acetylcysteine or nitroglycerin alone. The combination of nitroglycerin and N-acetylcysteine was associated with a high incidence of side effects (35%), mainly intolerable headache, which was almost twice as frequent as in patients receiving nitroglycerin alone. CONCLUSIONS: The combination of nitroglycerin and N-acetylcysteine, associated with conventional medical therapy in the long-term treatment of patients with unstable angina, reduces the occurrence of outcome events. However, the high incidence of side effects limits the clinical applicability of this therapeutic strategy at least at the dosage used in the present study.

Coronary atherosclerotic plaques with and without thrombus in ischemic heart syndromes: a morphologic, immunohistochemical, and biochemical study.

We investigated incidence, severity, and distribution of coronary atherosclerosis, acute thrombosis, and plaque fissuring in ischemic heart disease (both unstable-acute syndromes and chronic ischemia) and in nonischemic controls. We also studied the structural, immunohistochemical, and biochemical profile of plaques, with and without thrombus, including morphometry, immunophenotyping of inflammatory infiltrates, cytokine presence, and ultrastructural features. Critical coronary stenosis was almost the rule in both acute and chronic ischemic series (greater than 90%) whereas it reached 50% in control subjects. Thrombosis was principally characteristic of unstable-acute ischemic syndromes (unstable angina, 32%; acute myocardial infarction, 52%; cardiac sudden death, 26%) but was also found in chronic ischemia (stable angina, 12%; ischemic cardiomyopathy, 14%) and in control subjects (4%). Plaque fissuring without thrombus occurred in low percentages in lipid-rich, severe eccentric plaques in most series. Major differences were found between pultaceous-rich versus fibrous plaques rather than between plaques with or without thrombus. Pultaceous-rich plaques were frequent in sites of critical stenosis, thrombosis, and ulceration. Inflammatory infiltrates, i.e., T cells, macrophages, and a few beta cells, mostly occurred in lipid-rich, plaques unrelated to thrombus. In adventitia, infiltrates were a common finding unrelated to any syndrome. Necrotizing cytokines such as alpha-TNF were immunohistochemically detected in macrophages, smooth muscle, and intimal cells and detected by immunoblotting in 67% of pultaceous-rich plaques, either with or without thrombus. Immune response mediators such as IL-2 were also expressed in analogous plaques but in a minor percentage (50%-40%). Media were extensively damaged in severely diseased vessels with and without thrombus. Ultrastructural study showed that the fibrous cap was either highly cellular or densely fibrillar. Intimal injury with collagen exposure was often associated with platelet adhesion, whereas foamy cell exposure was not. In conclusion, investigated parameters were essentially similar in plaques, both with and without thrombus, whereas major differences were found between pultaceous-rich and fibrous plaques. Since platelets adhere to exposed collagen and not to foam cells, the type of exposed substrates could play a major role in thrombosis.

Ventricular septal rupture after myocardial infarction: diagnosis by two-dimensional and pulsed Doppler echocardiography.

Rupture of the ventricular septum in the acute phase of myocardial infarction (MI) requires prompt recognition for correct management. The 2-dimensional and pulsed Doppler echocardiographic findings are reported from 11 patients with ventricular septal (VS) rupture. VS rupture was confirmed by cardiac catheterization in 9 patients, surgery in 4 patients and necropsy examination in 3 patients. Two-dimensional echocardiography (echo) directly visualized the rupture in 7 patients and assessed the size and location of an associated aneurysm in 10. In all patients, M-mode pulsed Doppler echo allowed detection of the left-to-right shunting due to VS rupture, but failed to indicate the rupture site. M-mode pulsed Doppler echo was reliable for detecting VS rupture after MI. Conversely, 2-dimensional echo was less effective in the direct visualization of the rupture, but provided anatomic and functional information that was useful in medical and surgical management. Thus, the techniques are complementary and should be used in combination for the assessment of VS rupture in acute MI.

Significance of exercise-induced ST-segment elevation in patients without myocardial infarction.

Sixteen patients with exercise-induced ST-segment elevation and without a history of myocardial infarction or left ventricular aneurysm were studied. Fourteen complained of angina at rest, which was associated with ST-segment elevation in the same leads where it was recorded during exercise, and two patients had only exertional angina. Exercise-induced ST-segment elevation was generally reproducible in subsequent exercise tests performed in different hours of the day, but exercise tests repeated a mean of 15 months later did not induce this electrocardiographic abnormality. All patients had a marked susceptibility to coronary spasm, as shown by the response to the ergonovine test (12 positive tests in 12 patients) and by the occurrence of spontaneous spasm during coronary arteriography in two patients. In addition, coronary arteriography, performed in seven patients at the time of exercise-induced ST-segment elevation, revealed spasm of a major coronary vessel in all. In two patients we documented that exercise-induced ST-segment elevation was accompanied by a decreased coronary blood flow and increased coronary vascular resistance. We conclude that exercise-induced ST-segment elevation in patients without a history of myocardial infarction or left ventricular aneurysm is caused by coronary spasm of a major coronary vessel.

[Angina at rest. Clinical, electrocardiographic and angiographic observations in 107 patients]. / Angina a riposo. Osservazioni cliniche, elettrocardiografiche e angiografiche in 107 pazienti.

107 patients suffering from angina at rest associated with ST segment changes underwent coronary arteriography. 46 patients showed ST segment elevation during ischemic attacks (group I) while 61 patients exhibited ST segment depression during chest pain (group II). Non-significant coronary artery disease was more frequent in group I patients (group I 15%, group II 5%) as well as one vessel disease (group I 33%, group II 15%) while multivessel disease and left main involvement were more frequent in group II patients (group I 28%, group II 60%). Depression of left ventricular function was found in similar percentage of cases in both groups. During hospitalization all patients were treated with calcium antagonists (Nifedipine 10/20 mg every six hours) and/or nitrates (2% nitroglycerin ointment 2 inches every six/four hours) with one death (occurring after coronary arteriography) and eleven non-fatal myocardial infarctions. 50 patients underwent coronary bypass grafting with four perioperative deaths and six nonfatal myocardial infarctions. Most of the surgically treated patients were poorly responsive to medical treatment and had multivessel disease or left main involvement. Since these features are known to be related to a poor prognosis with medical treatment, surgical results in such patients seem satisfactory.