Stone heart: An unusual case of heart failure with preserved ejection fraction due to massive myocardial calcification.

We report an unusual case of heart failure due to massive myocardial calcification related to a rare combination of idiopathic mitral annular calcification, myocardial calcification of the left ventricular septum and the inferior wall without other predisposing factors, such as previous myocardial infarction, ventricular aneurysms, myocarditis, rheumatic heart disease, tuberculosis, chronic renal failure, or systemic metabolic disease (sarcoidosis or primary hyperoxaluria). The related restrictive pattern of diastolic filling of the left ventricle could explain this unusual case of heart failure with preserved ejection fraction. .

Syncope in a patient with acute pulmonary embolism and Brugada Type-2 ECG pattern: Brugada phenocopy or Brugada syndrome?

Brugada phenocopies are clinical entities characterized by electrocardiographic patterns that are identical to true Brugada syndrome, but are elicited by a number of clinical circumstances. ECG normalizes upon resolution of underlying condition, family history of arrhythmic syncope or ventricular arrhythmias is strictly absent and provocative tests with sodium channel blockers have to be negative. We describe herein the case of type-2 ECG Brugada pattern in a patient with acute pulmonary embolism presenting with recurrent syncope but negative provocative test with sodium channel blockers. Transthoracic echocardiography and transcranial Doppler did not show atrial septal defect. In conclusion, to the best of our knowledge no other cases excluded atrial septal defect and paradoxical embolism as a possible cause of acute pulmonary embolism related Type-2 Brugada ECG pattern. Therefore in our case right ventricle transmural myocardial ischemia due to acute pulmonary embolism, mainly secondary to right ventricle stretch, could explain Brugada ECG pattern.

Relationship between sRAGE and eotaxin-3 with CRP in hypertensive patients at high cardiovascular risk.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in Western countries and is highly prevalent in patients with kidney disease. Traditional risk factors for CVD often accompany kidney dysfunction, and chronic kidney disease per se is considered an additional risk factor. Risk stratification for CVD remains suboptimal even after the introduction of global risk assessment by various scores. This has prompted the search for novel markers of cardiovascular risk, and several biomarkers have been suggested as candidates, together with C-reactive protein (CRP). The objective of the present study was to investigate the relationship between novel biomarkers of vascular inflammation (soluble form of the receptor for advanced glycation end products [sRAGE] and eotaxin-3) with CRP in a population of hypertensive patients at high cardiovascular risk. METHODS: Plasma sRAGE, high-sensitivity CRP (hs-CRP) and eotaxin-3 were measured in 399 hypertensive patients (265 men, mean age 58 ± 8 years)with diabetes mellitus, metabolic syndrome or organ damage. RESULTS: Plasma concentrations of sRAGE, eotaxin-3 and hs-CRP were not different between diabetic and nondiabetic subjects. Univariate analysis showed that plasma levels of sRAGE and eotaxin-3 were not associated with hs-CRP in either subgroup. CONCLUSION: Our study confirms the robust and widely studied role of CRP as an important marker of vascular inflammation. We also postulate the possible involvement of sRAGE and eotaxin, 2 novel biomarkers, in CVDs. On the basis of our results, we can put forward the hypotheses that hs-CRP, s-RAGE and eotaxin are reliable but unrelated cardiovascular risk markers.

Microalbuminuria and sRAGE in high-risk hypertensive patients treated with nifedipine/telmisartan combination treatment: a substudy of TALENT.

Some antihypertensive drugs have also renoprotective and anti-inflammatory properties that go beyond their effect on blood pressure. It has been suggested that microalbuminuria and glomerular filtration rate (GFR) are associated with circulating levels of the soluble form of the receptor, sRAGE (soluble receptor for advanced glycation ends-products). In the present analysis, we used data from the TALENT study to evaluate soluble receptor for advanced glycation end-products (sRAGE) plasma levels in patients with hypertension and high-cardiovascular risk-treated nifedipine and telmisartan in combination. Treatment with nifedipine-telmisartan significantly decreased mean systolic and diastolic ambulatory blood pressure and resulted in a significant increase in sRAGE plasma concentrations after 24 weeks of therapy. We concluded that in hypertensive patients with early-stage renal disease, sRAGE concentrations are not influenced by either microalbuminuria or GFR. Long-term treatment with a combination of nifedipine-telmisartan may have a beneficial effect increasing sRAGE plasma levels, thus exerting an atheroprotective and anti-inflammatory activity.

APJ polymorphisms in coronary artery disease patients with and without hypertension.

Apelin is an endogenous peptide that increases cardiac inotropism through its APJ receptor. Certain findings indicate that the apelinergic system may have a pathophysiological role in cardiovascular disease and there is evidence showing the role of the apelinergic system in blood pressure regulation in vitro and in animal models. The role of the apelin-APJ system in cardiovascular physiology and its interaction with other neuroendocrine pathways has not been fully elucidated. However, the small number of reported studies indicates that apelin signaling may be involved in the regulation of blood pressure, cardiac contractile function, fluid balance, angiogenesis and inhibition of apoptosis. We evaluated the possible relationship between the G212A and A445C APJ polymorphisms and coronary artery disease (CAD) in Italian patients and in healthy controls by RFLP-PCR. We analyzed the allelic and genotypic frequencies of APJ polymorphisms in 664 patients (378 with hypertension) and 143 controls. There were no differences between allelic and genotypic frequencies in patients in respect to the controls for both polymorphisms analyzed. In the CAD population, there was an increased frequency of the G212 allele in patients with hypertension in respect to patients without hypertension. No differences were present in the two subgroups for the A445C polymorphism. Although the functional role of the G212A polymorphism has not yet been identified, it is possible to hypothesize that the presence of the A allele may cause a gain in function of the apelin/APJ system associated with a lower risk of hypertension.

Age of onset of myocardial infarction: is promoter polymorphism of the RAGE gene implicated?

Receptor for advanced glycation endproducts (RAGE) is a cell-surface molecule member of the immunoglobulin superfamily and engages differing ligands relevant to distinct processes. A growing body of evidence has suggested that RAGE may promote vascular inflammation through several mechanisms. The objective of this study was to identify the possible relationship between the -374 T/A polymorphism of the RAGE gene, myocardial infarction (MI), and its age of onset. A total of 691 MI patients and 234 matched controls were investigated. In this study, the frequency of the A allele and AA genotype of the -374 T/A promoter polymorphism is significantly lower in patients with MI respect to the control group (p < 0.01). Our results showed a significant role of the AA genotype on age of onset of MI. In particular, the mean age of the first MI was higher in patients with the AA genotype as compared to those that were AT or TT genotype carriers (p = 0.002). The relationship between -374 T/A RAGE polymorphism and age for the appearance of MI was independently related to common risk factors of disease (p < 0.01). Kaplan-Meier curves confirmed that subjects with the AA genotype have a later development of MI (p = 0.0022). This study is the first to investigate the role of RAGE polymorphisms on the susceptibility to develop the acute coronary events in the Italian population and identified this polymorphism as an age-related factor for MI development. The homozygous AA genotype may exert a protective role against the early development of MI.

[Non-pharmacological therapy of decompensated heart failure: cardiac resynchronization therapy]. / Terapia non farmacologica dell'insufficienza cardiaca: la resincronizzazione.

Cardiac resynchronization therapy (CRT) is a novel and effective therapy for patients with heart failure. The aim of CRT is to improve the heart's pumping efficiency by the resynchronization of the chambers. Electrical dyssynchrony shows itself as bundle branch block with prolongation of QRS >120 ms. Mechanical dyssynchrony (atrioventricular, interventricular and intraventricular) is evidenced by echocardiographic parameters. A cardioverter-defibrillator function can be included with the pulse generator in patients with high risk of sudden death. The estimate of perioperative death associated with CRT was 0.3% with a low rate of complications, similar to that seen in standard pacemaker placement. In 10% of patients there was an implant failure due to the difficulty in accessing the coronary sinus. Approximately one third of patients are non-responder with no significant improvement after implantation. The beneficial effect of CRT on soft endpoints and mortality (symptoms, NYHA class, 6-min walking test, quality of life score, ejection fraction) was demonstrated in the earliest randomized clinical trials. Current guidelines for CRT are based on inclusion and exclusion criteria in the large randomized trials that have been performed and patients with chronic atrial fibrillation are included. Unresolved issues are the identification of non-responders and the efficacy of CRT in patients with mechanical dyssynchrony without electrical dyssynchrony and in NYHA functional class I/II patients with ejection fraction < or = 35%.

Rapid heart rate increase at onset of exercise predicts adverse cardiac events in patients with coronary artery disease.

BACKGROUND: We previously demonstrated that reduced vagal activity and/or increased sympathetic activity identify post-myocardial infarction patients at high risk for cardiac mortality. Simple and inexpensive autonomic markers are necessary to perform autonomic screening in large populations. We tested our hypothesis that abnormally elevated heart rate (HR) responses at the onset of an exercise stress test, which imply rapid vagal withdrawal immediately preceding sympathetic activation, might predict adverse cardiac events in patients with documented coronary artery disease. METHODS AND RESULTS: The HR increase during the first minute (DeltaHR1 minute) of a symptom-limited exercise stress test was quantified in 458 patients with documented coronary artery disease. During a 6-year (interquartile range 3.7 to 9.0 years) follow-up, 71 patients experienced adverse cardiac events (21 cardiac deaths, 56 nonfatal myocardial infarctions). In univariate analysis, DeltaHR1 minute > or =12 bpm (above the median value of its distribution) predicted both adverse outcome and cardiac death with a hazard ratio of 5.0 (95% CI 2.7 to 9.1; P<0.0001) and of 15.6 (95% CI 2.0 to 118.7; P<0.001), respectively. After adjustment for potential confounders, DeltaHR1 minute remained predictive for both combined end points and for cardiac death. CONCLUSIONS: A marked HR increase at the onset of a standard exercise stress test is a novel and easily available parameter that could be clinically useful as an independent predictor of adverse cardiac events, including death, among patients with documented coronary artery disease.