Transcatheter aortic valve replacement and stroke: a comprehensive review.

Transcatheter aortic valve implantation (TAVR) has emerged as an alternative, rapidly evolving treatment option for patients with severe aortic stenosis and high surgical risk. Stroke is a devastating complication being confined mainly in the periprocedural and 30-day period following TAVR, with a lower and relatively constant frequency thereafter. Early stroke is mainly due to debris embolization during the procedure, whereas later events are associated with patient specific factors. Despite the fact that the rate of clinical stroke has been constantly decreasing compared to initial TAVR experience, modern neuro-imaging with MRI suggests that new ischemic lesions post-TAVR are almost universal. The impact of the latter is largely unknown. However, they seem to correlate with a reduction in neurocognitive function. Because TAVR is set to expand its indication to lower surgical-risk patients, stroke prophylaxis during and after TAVR becomes of paramount importance. Based on clinical and pathophysiological evidence, three lines of research are actively employed towards this direction: improvement in valve and delivery system technology with an aim to reduce manipulations and contact with the calcified aortic arch and native valve, antithrombotic therapy, and embolic protection devices. Careful patient selection, design of the procedure, and tailored antithrombotic strategies respecting the bleeding risks of this fragile population constitute the main defense against stroke following TAVR.

Calcium Homeostasis and Kinetics in Heart Failure.

Although HF has multiple causes amongst which coronary artery disease, hypertension and non-ischemic dilated cardiomyopathy are the most common, it results in the same final common pathway of neurohormonal activation and multiorgan dysfunction in the context of a salt-avid state. Contemporary pharmacologic HF therapy targets neurohormonal activation at multiple levels with ß- blockers, angiotensin converting enzyme inhibitors, and aldosterone inhibitors, aiming in reversing both its systemic consequences, and the adverse heart remodeling, however is frequently hampered by side effects of the drugs, limiting its benefit. During the last 40 years studies of the gross and molecular aspects of the pathophysiology of HF convincingly converge to the conclusion that deranged calcium (Ca(2+)) handling in the cardiomyocytes plays a cardinal role in HF initiation and progression. The delicate and precise regulation of Ca(2+) cycling i.e. movement into and out of the cell, as well as into and out of the sarcoplasmic reticulum (SR), is finely tuned by numerous macromolecular proteins and regulatory processes like phosphorylation and dephosphorylation, and is severely deranged in HF. The common denominator in this scenario is Ca(2+) depletion of the SR, however loading of cardiomyocytes with Ca(2+) as a result of classic inotropic therapy has proved to be detrimental in the long term. Therefore, the mediator and/or regulatory components of the Ca(2+) cycling apparatus have been the focus of extensive research involving targeted pharmacologic and gene interventions aiming to a restoration of Ca(2+) cycling processes, thus improving inotropy and lucitropy in a more "physiologic" way in the failing myocardium.

Neurohormonal activation and its relation to outcomes late after repair of tetralogy of Fallot.

BACKGROUND: Brain natriuretic peptide (BNP) levels are elevated in patients with repaired Tetralogy of Fallot (rTOF), the clinical significance of which remains uncertain. METHODS AND RESULTS: Ninety consecutive adults (≥ 16 years) with rTOF (mean age 32.7 ± 11.3 years, 64% men) were prospectively recruited from a single tertiary centre, together with 15 age-matched and gender-matched controls. Patients with rTOF had elevated BNP (8.9 (5.9-14.6) vs 5.4 (2.2-7.5) pmol/L; p<0.01), and BNP activation was common even in asymptomatic patients. Also, atrial natriuretic peptide (6.9 (4.0-9.9) vs 3.3 (1.0-4.0) pmol/L; p<0.01), endothelin-1 (1.14 (0.94-1.48) vs 0.75 (0.44-0.93) pmol/L; p<0.01) and renin (55.0 (45.5-66.5) vs 18.6 (12.0-22.7) pmol/L; p<0.01) were elevated at baseline compared with controls. Interactions between BNP with endothelin-1, cardiothoracic ratio and right atrial area were evident. Eight deaths occurred over a median follow-up of 10 years. On Cox regression analysis, BNP emerged as a strong predictor of death (HR 1.16 per 10 pmol/L, 95% CI 1.05 to 1.29; p<0.01). Survival receiver operating curve analysis revealed an optimum cut-off of BNP ≥ 15 pmol/L (=52 pg/mL), above which BNP was related to significantly increased mortality (HR 5.40, 95% CI 1.29 to 22.6; p<0.01); absolute mortality at 5 years 19% vs 3% in patients with BNP ≤ 15 pmol/L. BNP was also a predictor of sustained arrhythmia (HR 2.06 per 10 pmol/L, 95% CI 1.32 to 3.21; p<0.05). CONCLUSIONS: Neurohormonal activation is present in adults with rTOF including asymptomatic patients. BNP level ≥ 15 pmol/L is associated with a fivefold increased risk of death. These data suggest that BNP measurement in patients with rTOF should be incorporated in the periodic risk stratification assessment of these patients under lifelong follow-up.

Heterogeneity of ventricular repolarization in newborns with intrauterine growth restriction.

BACKGROUND: Intrauterine growth restriction (IUGR) is associated with structural and functional cardiac alterations but the electrophysiological consequences of these disturbances remain unknown. AIMS: To explore the distribution of ventricular repolarization and its relation to myocardial mechanics in newborns with IUGR. STUDY DESIGN, SUBJECTS AND OUTCOME MEASUREMENTS: Conventional and tissue Doppler echocardiographic data, and electrocardiographic parameters used to describe the distribution of ventricular repolarization (dispersion of QT [QTd] and JT [JTd]), were obtained on the second (D2) and fifth (D5) postnatal day and compared between 25 IUGR newborns and 25 matched-for-gestational age controls. RESULTS: IUGR was associated with relative interventricular septum hypertrophy, increased left ventricular (LV) E/E' ratio and higher LV myocardial performance index (MPI). On both study days, the IUGR infants presented higher QTd and JTd compared to controls (QTd-D2: 66±20 ms vs. 36±12 ms, P<0.001; JTd-D2: 54±13 ms vs. 34±9 ms, P<0.001; QTd-D5: 61±14 ms vs. 27±12 ms, P<0.001; JTd-D5: 54±13 ms vs. 27±9 ms, P<0.001). The association between QTd and LV E/E' (D2: regression coefficient beta 0.747, R(2) 0.585; D5: beta 0.843, R(2) 0.646) and QTd and MPI (D2: beta 0.680, R(2) 0.576; D5: beta 0.698, R(2) 0.650) was also significant (P<0.001 for all analyses). CONCLUSIONS: Our findings suggest that IUGR is associated with electrophysiological remodeling of the neonatal heart, a process which is closely related to the underlying alterations in ventricular mechanics and might predispose to adverse electrophysiological events.

Neonatal cardiac dysfunction in intrauterine growth restriction.

BACKGROUND: The early postnatal cardiovascular consequences of intrauterine growth restriction (IUGR) have not been completely elucidated. This study aimed to evaluate the effect of IUGR on neonatal myocardial function and cardiovascular adaptation to extrauterine life. METHODS: Conventional and tissue Doppler echocardiographic parameters were compared on the second and fifth postnatal day between 30 IUGR and 30 appropriate-for-gestational age (AGA) neonates. RESULTS: IUGR neonates presented relative interventricular septum (IVS) hypertrophy (IVS to left ventricular (LV) posterior wall diastolic ratio: median IUGR-AGA difference of 0.05 (interquartile range: 0.04-0.06); P = 0.020), relative LV dilatation (wall thickness to end-diastolic LV dimension difference of 0.12 (0.06-0.16); P = 0.012), and increased left myocardial performance index (MPI difference of 0.19 (0.05-0.28); P = 0.012). Repeated measurements ANOVA revealed a different pattern of change in LV stroke volume (LVSV; P < 0.001), LV cardiac output (LVCO; P < 0.001), MPI (P < 0.001), and heart rate (HR; P = 0.025) between AGA and IUGR infants. From the second to the fifth postnatal day, AGA neonates presented a decrease in MPI and HR with an increase in LVSV and LVCO. IUGR neonates failed to achieve similar changes in MPI, HR, and LVSV, whereas their LVCO decreased. CONCLUSION: IUGR neonates present changes in cardiac morphology and subclinical myocardial dysfunction, which may result in an altered pattern of cardiovascular adaptation to extrauterine life.

Thrombus extraction catheters vs. angiojet rheolytic thrombectomy in thrombotic lesions/SV grafts.

Primary percutaneous coronary intervention, (pPCI), of native coronaries and saphenous vein grafts (SVGs), is the recommended reperfusion strategy for STEMI, and an early invasive approach is recommended for high risk patients with UA/NSTEMI. Although PCI effectively restores flow in the infarct related artery/culprit vessel in both situations, myocardial perfusion often remains suboptimal due to microvascular obstruction, partly attributed to distal embolization of thrombus. Hence, thrombectomy (manual or mechanical), prior to stenting may further reduce hard clinical end points in patients with ACS. This article discusses accumulated evidence regarding the safety and effectiveness of thrombectomy in culprit native coronaries and SVGs in such patients, as well as possible strategies for maximizing its benefits relative to the size of the thrombotic burden.

Randomised trial of ramipril in repaired tetralogy of Fallot and pulmonary regurgitation: the APPROPRIATE study (Ace inhibitors for Potential PRevention Of the deleterious effects of Pulmonary Regurgitation In Adults with repaired TEtralogy of Fallot).

BACKGROUND: Optimal treatment for stable repaired tetralogy of Fallot (rTOF) patients with pulmonary regurgitation (PR) and related right ventricular (RV) dilatation, including timing of valve implantation, remains uncertain. We sought to study tolerability of the angiotensin-converting-enzyme (ACE) inhibitor ramipril and its effects on cardiovascular function in these patients. METHODS: Clinically stable rTOF patients with moderate/severe PR were included. A double-blinded, placebo-controlled study of 6 months of ramipril vs placebo was performed. All patients underwent cardiovascular magnetic resonance (CMR), echocardiography, neurohormonal analysis, and objective cardiopulmonary exercise testing at baseline and follow-up. PRIMARY ENDPOINT: The main aim was to detect changes in RV function (primary endpoint CMR-derived RV ejection fraction). RESULTS: Seventy-two patients were enrolled and 64 qualified for the final analysis. There was no difference in the primary endpoint RV ejection fraction. RV long-axis shortening significantly improved in the ramipril group compared to placebo (RV: 2.3 ± 3.8 vs 0.02 ± 2.7 mm; P=0.017) as did LV long-axis shortening (1.9 ± 4.5 vs -0.2 ± 3.7 mm respectively; P=0.030). No clear differences were detected between ramipril and placebo for other measures. In a subgroup of patients with restrictive RV physiology, ramipril resulted in decrease in LV end-systolic volume index and increase in LVEF (-2.4 ± 5.0 vs 2.7 ± 3.6 mL/m(2); P=0.005, 2.5 ± 5.0 vs -1.3 ± 3.5%; P=0.03). Ramipril did not cause adverse events and was well tolerated. CONCLUSIONS: Ramipril is a well tolerated therapy, improves biventricular function in patients with rTOF and may have a particular role in patients with restrictive RV physiology. Larger, longer-term studies are needed to determine if ACE inhibitors can improve both ventricular remodelling and clinical outcomes. ( ISRCTN: 97515585).

An optical coherence tomography study of two new generation stents with biodegradable polymer carrier, eluting paclitaxel vs. biolimus-A9.

BACKGROUND: Tissue coverage and strut apposition of drug eluting stents (DES), which can be assessed with optical coherence tomography (OCT), may be associated with late stent thrombosis (LST). METHODS: Prospective observational angiographic and OCT follow-up at 6 months post-implantation of a biolimus-A9 eluting stent (BES) vs. a paclitaxel eluting stent (PES), with biodegradable polymer carriers. The primary outcome was the percent difference of uncovered struts between BESs and PESs. RESULTS: A maximum likelihood model was used for analysis, to account for data clustering. Sixteen patients were treated with BES (28 lesions/4530 struts) and 16 with PES (23 lesions/4450 struts). Overall, BESs compared to PESs had more uncovered [0.41% vs. 0.21%, difference estimate (DE) 0.2 (95% CI, 0.06-0.34), p=0.006], malapposed [0.18% vs. 0.04%, DE 0.14 (95% CI 0.05-0.23), p=0.003], uncovered and malapposed [0.08% vs. 0.026%, DE 0.057 (95% CI 0.015-0.1), p=0.01] and protruding struts [0.23% vs. 0.04%, DE 0.185 (95% CI 0.1-0.27), p<0.001], and significantly lower neointimal thickness (59.3 ± 28.2 µm vs. 201.7 ± 97.5, p<0.001). None of the BESs was totally covered with neointima, in contrast to 5 (21.7%) PESs (p=0.01). Thrombus was detected in 1 (3.6%) BES and 5 (21.7%) PESs (p=0.05); however, no patient experienced clinical stent thrombosis. CONCLUSION: Between two stents with biodegradable polymer, OCT demonstrated that BESs had more uncovered and malapposed struts compared to PESs at 6 months. This difference might be partly attributed to the more potent antiproliferative properties of biolimus-A9; however, its impact on clinical outcome and on the risk of LST is yet to be determined.

Flat panel digital detector cinefluoroscopy late following SES or BMS implantation for detection of coronary stent fracture in asymptomatic patients.

BACKGROUND: Coronary stent fracture (SF), is rare and confined mainly in patients treated with sirolimus eluting stents (SES). The role of flat panel digital detector (FPDD) fluoroscopy in detecting SF has not been investigated. METHODS: Assessment with FPDD fluoroscopy of asymptomatic patients, with 200 SES (Cypher, Cordis, J&J, Miami, Florida, US), and 200 bare metal stents (BMS), at 45.5 ± 15.7 and 38.4 ± 3.9 months post-stenting respectively. SF was defined as discontinuity of stent struts on fluoroscopy. Coronary angiography was reserved for patients with documented SF. RESULTS: Effective radiation dose was 0.26 ± 0.14 mSv. SF was depicted in 6 (3%) SES, and 1 BMS (0.5%). Stent length was an independent predictor of SF (OR 1.19, 95% CI 1.03-1.4, p=0.024). RCA location and vessel angulation were marginally significant (OR 7.7, 95% CI 0.8-74.2, p=0.077 and OR 5.1, 95% CI 0.8-34, p=0.089). Significant angiographic restenosis was detected in 4 SES (66.6%), and 1 BMS (0.5%). Re-intervention was needed in 3 (42.8%) cases, (2 SES and 1 BMS). CONCLUSION: Detection of SF with FPDD cinefluoroscopy late following coronary stenting is feasible, involves low radiation and is confined mainly to SES compared to BMS. Application of cinefluoroscopy as part of a routine stent surveillance programme in asymptomatic patients may be more appropriate in "high risk" settings (SES, long stents and adverse angiographic characteristics). The role of invasive imaging and subsequent management of such patients need further studying.

Mechanisms of non-fatal stent-related myocardial infarction late following coronary stenting with drug-eluting stents and bare metal stents. Insights from optical coherence tomography.

BACKGROUND: A prospective observational study using optical coherence tomography (OCT) of patients with myocardial infarction (MI), late following drug-eluting (DES) or bare metal stent (BMS) implantation, when the stented segment was considered culprit. METHODS AND RESULTS: Seventeen patients (58.9±8.3 years; 7 DES, 10 BMS) with MI at 50 (3-180) months post-stenting. Patients with BMS sustained a MI later than patients with DES (95 (3-180) vs. 8 (3-62) months, P=0.01]; 5 (71.4%) of the DES patients demonstrated binary angiographic restenosis, in contrast to 8 (80%) with BMS (P=1.0). DES had significantly less thickness of the neointimal hyperplasia compared with BMS (0.08±0.04 vs. 0.36±0.2mm, P=0.003). None of the DES was totally covered with neointimal tissue. The overall percentage of uncovered and malapposed struts (ANCOVA), was significantly higher in DES than BMS (1.96, 95% confidence interval (CI) 1.5-2.4 vs. 0.25, 95%CI 0.1-0.6, P<0.001, and 0.66, 95%CI 0.29-1.03 vs. 0.11, 95%CI 0.19-0.4, P=0.03, respectively). OCT features of atherosclerosis (lipid, neovascularization, or calcification) and possible neointimal rupture were found only in patients with BMS. Thrombus detection was not different between the 2 groups. CONCLUSIONS: Stent-related, non-fatal, late acute MI following stent implantation occurs later in patients with a BMS compared with those with a DES, and the mechanism includes delayed healing (mainly DES), and neointimal hyperplasia with atherosclerotic transformation and subsequent rupture (mainly BMS).

Congenital left main coronary artery to coronary sinus fistula.

Congenital coronary artery fistula is an extremely rare anomaly that may involve any of the coronary arteries and any of the cardiac chambers. We report the case of a 14-year-old female patient with a symptomatic congenital coronary fistula starting from the left main coronary artery and draining to the coronary sinus. The patient underwent surgical ligation of the fistula and had an excellent outcome.

An unusual case of cor triatriatum sinister presenting as pulmonary oedema during labor.

A 35 years old second gravida was admitted to our department with acute pulmonary oedema after labor. Echocardiography disclosed an intra-atrial membrane prolapsing through the mitral valve in diastole, with two small orifices creating a mean pressure gradient of 7.9 mm Hg. However the membrane clearly originated away from the mitral valve ring, proximal to the left atrial appendage, consistent with cor triatriatum sinister. Cor triatriatum sinister rarely presents in adulthood and although forward movement of the membrane towards the mitral valve funnel has been described, such a degree of prolapse through the valve has never been reported.

Late asymptomatic sirolimus-eluting stent fracture in a female with systemic lupus erythematosus.

We report a case of a sirolimus eluting (Cypher, Johnson-Johnson) stent fracture (SF) incidentally depicted 3 years post PCI in an asymptomatic female with systemic lupus erythematosus (SLE). The vessel was assessed with intravascular ultrasound (IVUS) and optical coherence tomography (OCT). Different imaging modalities results are presented. OCT may offer superior imaging of SF compared to fluoroscopy and IVUS and might prove useful for the detailed assessment and tailored treatment of this rare complication.

Diagnostic role of plasma BNP levels in neonates with signs of congenital heart disease.

BACKGROUND: Only a few studies have examined the relationship of plasma BNP levels and congenital heart disease (CHD) in neonates and these mainly concern preterm neonates with patent ductus arteriosus. We aimed to investigate the diagnostic role of plasma BNP in neonates admitted in the neonatal intensive care unit, (NICU), with signs of congenital heart disease (CHD). METHODS: Prospective assessment of plasma BNP levels in 75 consecutive neonates with suspected CHD (heart murmur, respiratory distress, or cyanosis), admitted in the NICU of our university hospital. The final diagnosis was done with echocardiography. RESULTS: Haemodynamically significant Left to Right shunts, (hsLtR), were found in 29 neonates, insignificant LtR shunts in 22, no heart disease in 15 and cyanotic heart disease in 9. BNP levels were significantly higher in neonates with hsLtR shunts vs. all other groups (logBNP 2.9 ± 0.5 pg/ml vs. 1.5 ± 0.4 pg/ml vs. 1.5 ± 0.3 pg/ml vs. 1.6 ± 0.2 pg/ml, p < 0.0001). Plasma BNP levels > 132.5 pg/ml had 93.1% sensitivity and 100% specificity for diagnosing hsLtR shunts (accuracy 99.6%). CONCLUSIONS: Plasma BNP is a reliable test for diagnosing hsLtR shunts in the NICU. This will alert the neonatologist for ordering an echocardiographic examination, or if the latter is not available, for transferring the neonate to an appropriate tertiary centre with neonatal-paediatric cardiology facilities. Normal BNP levels imply the absence of a significant LtR shunt, but may not exclude cyanotic heart disease.

Neointimal coverage and stent strut apposition six months after implantation of a paclitaxel eluting stent in acute coronary syndromes: an optical coherence tomography study.

OBJECTIVES: Prospective optical coherence tomography (OCT) study of strut apposition and neointimal hyperplasia thickness (NIH) of a paclitaxel eluting stent (PES), (Infinium, Sahajanand Medical Technologies Pvt Ltd.). BACKGROUND: Few data exist concerning neointimal coverage of PES. Uncovered and malapposed struts are more common following stenting in acute coronary syndromes (ACS) than in non-ACS lesions. METHODS: All consecutive patients with ACS, treated with the above PES for single native coronary lesions between August 2008 and January 2009, who consented to invasive follow-up with OCT at six months (N=13), were included. RESULTS: At 6 months no patient demonstrated angiographic restenosis. 3180 struts from 20 stents were analyzed, and 91.3% were covered with neointima (NIH 204.8 ± 159.5 µm). Standard statistics and least squares estimates (LSE) derived from a hierarchical ANCOVA model to take into account clustering effects are presented. Rate of uncovered struts was 8.6%, LSE 7.39 (95% CI 3.05-11.73), malapposed struts 2.2%, LSE 1.76 (95% CI 0.05-3.58), and protruding struts 2.9%, LSE 2.8 (95% CI 1.35-4.65). The proportion of uncovered malapposed struts was significantly higher compared to uncovered embedded struts (55.7% vs. 6.8%, p<0.01). In total, 5 (25%) PES were fully covered by neointima. No intracoronary thrombus or clinical events were detected. CONCLUSIONS: Six months after implantation of a specific PES in patients with ACS, most of the stents were only partially covered with neointima, especially at sites of strut malapposition or protrusion. These findings emphasize the need for optimal stent apposition during implantation and for prolonged dual antiplatelet therapy.

Repair of anomalous origin of right pulmonary artery from ascending aorta without cardiopulmonary bypass.

Anomalous origin of a pulmonary artery from the ascending aorta (AORPA) is a rare congenital cardiac malformation that needs prompt surgical repair; otherwise it is associated with poor prognosis. We describe 3 cases of AORPA that successfully underwent complete surgical correction without extracorporeal circulation.