Myocardial late gadolinium enhancement is associated with clinical presentation in Duchenne muscular dystrophy carriers.

BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked recessive disease that occurs in males leading to immobility and death in early adulthood. Female carriers of DMD are generally asymptomatic, yet frequently develop dilated cardiomyopathy. This study aims to detect early cardiac manifestation in DMD using cardiovascular magnetic resonance (CMR) and to evaluate its association with clinical symptoms. METHODS: Clinical assessment of DMD carriers included six minutes walk tests (6MWT), blood analysis, electrocardiography, echocardiography, and CMR using FLASH sequences to detect late gadolinium enhancement (LGE). T1-mapping using the Modified Look-Locker Inversion recovery (MOLLI) sequence was performed quantify extracellular volume (ECV). RESULTS: Of 20 carriers (age 39.47 ± 12.96 years) 17 (89.5 %) were clinically asymptomatic. ECV was mildly elevated (29.79 ± 2.92 %) and LGE was detected in nine cases (45 %). LGE positive carriers had lower left ventricular ejection fraction in CMR (64.36 ± 5.78 vs. 56.67 ± 6.89 %, p = 0.014), higher bothCK (629.89 ± 317.48 vs. 256.18 ± 109.10 U/l, p = 0.002) and CK-MB (22.13 ± 5.25 vs. 12.11 ± 2.21 U/l, p = 0.001), as well as shorter walking distances during the 6MWT (432.44 ± 96.72 vs. 514.91 ± 66.80 m, p = 0.037). 90.9 % of subjects without LGE had normal pro-BNP, whereas in 66.7 % of those presenting LGE pro-BNP was elevated (p = 0.027). All individuals without LGE were in the NYHA class I, whereas all those in NYHA classes II and III showed positive for LGE (p = 0.066). CONCLUSIONS: Myocardial involvement shown as LGE in CMR occurs in a substantial number of DMD carriers; it is associated with clinical and morphometric signs of incipient heart failure. LGE is thus a sensitive parameter for the early diagnosis of cardiomyopathy in DMD carriers. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01712152 Trial registration: October 19, 2012. First patient enrolled: September 27, 2012 (retrospectively registered).

Exhaled nitric oxide measurement to monitor pulmonary hypertension in a pneumonectomy-monocrotaline rat model.

The use of fractional exhaled nitric oxide (FeNO) has been suggested as a quantitative marker for pulmonary arterial hypertension (PAH) in humans. To further characterize FeNO in PAH we investigated this marker in a rodent model. Since there is no standardized technique for FeNO measurement in animals, we intended to reduce measuring errors and confounders of an existing published method by mathematical modification and tested its applicability in an NO-regulating therapy concept of PAH. Thirty-three male Sprague-Dawley rats underwent unilateral pneumonectomy and monocrotaline (MCT) injection and were observed for 49 days. A telemetric catheter was introduced into the left pulmonary artery to continuously record mean pulmonary arterial pressure (mPAP), and FeNO was assessed. After 35 days, animals were randomized to receive either oral l-arginine (300 mg/kg) in combination with tetrahydrobiopterin (20 mg/kg) therapy (n = 12) or vehicle (n = 11) daily over a period of 14 days. mPAP at baseline was 17.19 ± 9.62 mmHg, which increased to 53.1 ± 10.63 mmHg 28 days after monocrotaline exposure (P < 0.001). Using the modified technique, we found an inverse correlation between exhaled NO and pulmonary pressures before (r = -0.366, P = 0.043) and after MCT (r = -0.363, P = 0.038) as well as after therapy administration (r = -0.657, P = 0.02). Our modified technique proved robust in a rodent model, since valid and reproducible data were gained and showed an inverse correlation between exhaled NO and mPAP, whereas the existing method did not.

Effect of music on patients with cardiovascular diseases and during cardiovascular interventions : A systematic review.

BACKGROUND: The therapeutic effects of music have been known for thousands of years. Recently, studies with music interventions in patients with cardiovascular diseases yielded controversial results. The aim of this review is to provide an overview of the effects of receptive music intervention on the cardiovascular system. METHODS: We searched in PubMed, SCOPUS and CENTRAL for publications between January 1980 and May 2018. Primary endpoints were heart rate, heart rate variability and blood pressure. Secondary endpoints comprised respiratory rate, anxiety and pain. The quality of the studies was assessed by using the CONSORT statement and the Cochrane risk of bias assessment tool. A meta-analysis and subgroup analyses concerning music style, gender and region were planned. RESULTS: A total of 29 studies comprising 2579 patients were included and 18 studies with 1758 patients investigated the effect of music on patients undergoing coronary angiography or open heart surgery. Other studies applied music to children with congenital heart diseases, pregnant women with hypertension or patients with unstable angina. Due to high methodological study heterogeneity, a meta-analysis was not performed. The study quality was assessed as medium to low. In ten studies with higher quality comprising 1054 patients, music intervention was not associated with significant changes in the cardiovascular endpoints compared to the control group. The subgroup analyses did not demonstrate any relevant results. CONCLUSION: Currently no definite effect of receptive music intervention on the cardiovascular system can be verified. Further research is needed to assess music as an inexpensive and easy applicable form of therapy.

[Revascularization of coronary artery disease in diabetes mellitus]. / Revaskularisation der koronaren Herzerkrankung bei Diabetes mellitus.

Coronary artery disease in diabetes mellitus (DM) is still associated with a poor prognosis. Especially percutaneous coronary interventions (PCI) have a higher rate of complications and restenosis, so that surgical revascularization is usually favoured in DM. The development of drug-eluting stents has improved the results of PCI significantly, however, there are still not enough prospective data comparing them to bypass surgery. The present paper summarizes the current state of coronary revascularization.

Time course of prothrombotic and proinflammatory substance release after intracoronary stent implantation.

We hypothesized that restenosis after coronary stenting is predicted by elevated levels of markers of thrombus formation and inflammation. Plasma levels of representative markers of inflammation, the thrombin and plasmin activation systems and adhesion molecules were measured in 59 patients with stable angina pectoris before, immediately after and 6 hours (h), 12 h, 24 h, one month and six months after elective stent implantation (radioactive phosphorus-32 stents/RSs/ n = 16, bare-metal stents/BMSs/ n = 43). All patients underwent clinical and angiographic follow-up (FUP) six months after stenting. RSs had significantly higher angiographic severity of restenosis than BMSs (47.1 +/- 20.1% vs. 27.6 +/- 22.0%, p = 0.003). Repeated measures ANOVA revealed significant differences between the BMS and RS groups as regards the increases in plasma levels of vascular cell adhesion molecule-1 (VCAM-1, p = 0.022), plasminogen activator inhibitor-1 (PAI-1, p = 0.047), tissue-type plasminogen activator (tPA, p = 0.047) and CD40 ligand (CD40L, p = 0.038). tPA levels tended to increase immediately after stenting in both groups, whereas the PAI-1 level one month after stenting was elevated significantly only in the RS group. In the RS group, the plasma levels of CD40L were increased at 24 h and six months after stenting, and the VCAM-1 level rose immediately after stenting and remained high during the FUP. Multivariate analysis on pooled laboratory data of both groups revealed elevated levels of VCAM-1 at 12 h and at six months as significant predictors of the severity of stent restenosis. In conclusion, the process of inflammation and thrombosis occurring after coronary interventions seems to be prolonged and enhanced in patients with high-grade restenosis at the follow up.

Vascular morphometric changes after radioactive stent implantation: a dose-response analysis.

OBJECTIVES: The goal of this study was to evaluate the dose-dependency of morphometric changes in the coronary arterial wall after radioactive stenting. BACKGROUND: Radioactive stents have been found to reduce intrastent intimal hyperplasia (IIH) but lead to a characteristic type of restenosis occurring predominantly at the stent edges. METHODS: Fifteen patients underwent intravascular ultrasound (IVUS) examination after implantation of a P-32 radioactive stent and at the six-month follow-up. The post-stent IVUS measurements on seven predefined locations of each lesion were subjected to a computer algorithm for the development of dose-volume histograms (DVH). Thus, we derived the radiation doses delivered to at least 10% and 90% of the adventitia (DV10, DV90). The IIH and vascular remodeling at follow-up were correlated with the doses in each segment. RESULTS: The IIH was most pronounced at the stent edges and lowest in the stent-body, whereas we detected a significant expansive remodeling within the stent body. The delivered doses correlated with a decreased IIH (r = 0.52, p < 0.001 for DV10 and r = 0.62, p < 0.001 for DV90) and with expansive remodeling (r = 0.48, p = 0.009 for DV10 and r = 0.50, p = 0.006 for DV90). A DV10 >90 Gy or a DV90 >15 Gy reduced IIH and induced expansive remodeling. Plaque growth was not reduced by radioactive stents. CONCLUSIONS: The DVH analysis reveals a dose-dependent increase of external elastic lamina area behind radioactive stents, whereas plaque growth is not reduced but inverted into an outward direction from the stent. A DV10 >90 Gy or a DV90 >15 Gy results in a beneficial long-term outcome after radioactive stenting.

Geographical miss during intracoronary irradiation: impact on restenosis and determination of required safety margin length.

OBJECTIVE: The goal of this study was to evaluate the incidence and effects of underdosage of injured segments during intracoronary irradiation and to define the minimal length of safety margin required to avoid mismatched source placement. BACKGROUND: Underdosage of injured segments due to misplacement of active source has been suggested as the underlying mechanism for the occurrence of edge restenosis. METHODS: Baseline angiograms of 112 vessels in 109 patients with in-stent restenosis undergoing coronary reintervention followed by intracoronary irradiation ((192)Ir: Checkmate, Cordis, Miami, Florida; (32)P: Gallileo, Guidant, Houston, Texas; (90)Sr/Y: Beta-Cath, Novoste, Norcross, Georgia) were analyzed. The distances between the outermost injury and outermost end of "reference isodose length" (RIL), defined as a segment with >/=90% of reference dose at 1 mm vessel wall depth, were measured. "Safety margin" was defined as the distance between the outermost injury and outermost end of the RIL, "geographical miss" (GM) as a complete injured segment not being covered by the RIL, and "restenosis" as the percent diameter stenosis >50%. RESULTS: Baseline angiographic analysis was performed for 224 edges in 112 vessels. Geographical miss was found in 46 (20.6%) edges. The incidence of target lesion restenosis within the 78 vessels with available follow-up was 43.3% for patients with GM versus 14.9% for patients with no GM (p = 0.005). Analysis of various injured segments exposed highest restenosis rates in injured segments with negligible irradiation (27.8%) in comparison with injured segments with dose fall-off (16.7%) or injured segments with full-dose irradiation (7.7%) (p = 0.006). Receiver operating curve analysis revealed a safety margin of 10 mm required per vessel (i.e., 5-mm safety margin/edge) to achieve 95% specificity of GM. CONCLUSIONS: Geographical miss is associated with a higher incidence of restenosis at the corresponding edges. Restenosis was more pronounced in injured segments with negligible irradiation than in injured segments at the dose fall-off zones. We recommend a safety margin of 10 mm per vessel to minimize GM.

Determination and application of the reference isodose length (RIL) for commercial endovascular brachytherapy devices.

BACKGROUND AND PURPOSE: During the last years endovascular brachytherapy has been established as a new field in radiotherapy. In a recent recommendation of the EndoVAscular, Groupe Européen de Curiethérapie, European Society for Therapeutic Radiation Oncology, Working Group the reference isodose length (RIL) has been introduced as a central parameter for treatment planning. It is defined as the vessel length at the reference depth enclosed by the 90% isodose. The dose is normalized to 100% at the reference depth (i.e. lumen radius plus 1 mm into the vessel wall) at the central plane. In order to avoid a geographic miss the clinical target length has to be encompassed by the RIL. MATERIAL AND METHODS: RILs are determined by Monte Carlo calculations and GafChromic film dosimetry for three endovascular brachytherapy devices currently in clinical use (192Ir seed ribbon, 32P wire source, 90Sr seed train). For all measurements, phantoms and devices the sensitive layer of GafChromic film is located in a plane at 2+/-0.1 mm parallel to the axis of the source delivery catheter. The EGSnrc code system is applied to calculate the dose profile at 2 and 3 mm distance from the source axis. RESULTS: For the ten seed 192Ir source calculated RIL at 2 mm radial distance is 30.2 mm whereas the measured RIL is 33.5 mm. In case of a 20 mm 32P wire source with two steps the calculated RIL of 36.6 mm shows excellent agreement compared with the measured value of 36.2 mm. The calculated RIL of a 40 mm 90Sr seed train was 35.8 mm compared to a measured value of 34.8 mm. CONCLUSION: As a compromise between calculated and measured RIL values at 2 and 3 mm radial distances we propose to use a RIL of 30 mm for the 192Ir ten seed ribbon, 36 mm for the32P wire source with two steps and 35 mm for the 40 mm 90Sr seed train. These parameter values can be used to define the maximum intervention length for endovascular sources.

Quality assurance in intracoronary brachytherapy. Recommendations for determining the planning target length to avoid geographic miss.

BACKGROUND AND PURPOSE: A new method of assessing geographic miss (GM) in endovascular brachytherapy (EVBT) is applied to evaluate the quality of intracoronary brachytherapy treatments, retrospectively. Based on the Vienna experience, recommendations for adequate safety margins are derived to avoid GM. PATIENTS AND METHODS: Evaluation is done on 136 vessels of 128 consecutive patients treated between October 1999 and July 2001. The quality of EVBT is assessed using the concept and terminology of the EVA GEC ESTRO task group. Evaluation of GM and/or safety margin is performed by comparing the outermost interventions with the reference isodose length (RIL) of the applied delivering devices on recorded compact disk (CD) angiograms. The RIL is defined as the length of the vessel segment, which receives at least 90% of the reference dose at the reference depth (=1 mm within the vessel). GM is defined as injured vessel segments, which receive a dose lower than 90% of reference dose. Measurements of intervention length (IL) and active source length (ASL) are performed with respect to anatomical landmarks within the vessel in the region of interest (e.g. stent edges), and by using the nominal length of the devices (balloons, sources) as a reference scale. The edges of RIL are determined by subtracting the length of the dose-fall-off zone (specific to the applied delivery devices: (192)Ir 4.5 mm, (90)Sr 2.5 mm, (32)P 2.0 mm) from the edges of ASL. RESULTS: The described method to assess GM is applicable to 128 vessels (94%). GM is found in 23% of proximal edges and 20% of distal edges. 95% of all GM are observed if the total margin (proximal+distal margin) between RIL and IL is shorter than 10.5 mm. CONCLUSIONS: GM in intracoronary brachytherapy can be widely avoided by adding an appropriate safety margin to the IL (5-6 mm each edge in this study) in order to determine the necessary RIL for a treatment.

Intimal hyperplasia and coronary flow reserve after heart transplantation: association with big endothelin-1.

BACKGROUND: Endothelin, a peptide with strong vasoconstrictive and mitogenic properties, has been found to increase after cardiac transplantation. We therefore assessed the association between its precursor peptide, big endothelin-1, and intimal hyperplasia and coronary flow reserve after heart transplantation. METHODS: Thirty-five patients without hemodynamically significant coronary artery disease after heart transplantation were investigated: Average peak flow velocity in the left anterior descending artery (LAD) was assessed by intracoronary Doppler at baseline as well as after injection of adenosine; coronary flow reserve was calculated as a ratio of both and was corrected for patient age and baseline average peak flow velocity. Lumen, intima + media and total vessel area were measured by intracoronary ultrasound. The plasma concentration of big endothelin-1 in venous blood was determined by radioimmunoassay. RESULTS: Patients with elevated big endothelin-1 levels (>2 fmol/ml) tended to have a decreased corrected coronary flow reserve (2.60 +/- 0.9 vs 3.21 +/- 1.0, p = 0.078). They also had a significantly larger intima + media area (5.82 +/- 2.9 vs 2.37 +/- 2.9 mm(2), p = 0.004) and total vessel area (18.36 +/- 5.8 vs 12.81 +/- 4.8 mm(2), p = 0.012) than those with normal plasma concentrations. CONCLUSIONS: Our study suggests an association between elevated big endothelin-1 plasma levels and the development of intimal hyperplasia and reduction of coronary flow reserve after cardiac transplantation.

Mechanism of lumen gain during coronary stent deployment in diabetic patients compared with non-diabetic patients.

BACKGROUND: Diabetic patients show an increased incidence of restenosis after coronary angioplasty than non-diabetic patients. This may be because of differences in the mechanism of lumen gain during coronary revascularization in this population cohort. DESIGN: This study analyses the mechanism of lumen gain during coronary stent deployment in diabetic patients compared with non-diabetic patients with intravascular ultrasound (IVUS). METHODS: IVUS images were obtained prior to and after revascularization in 26 diabetic and 97 non-diabetic patients. The external elastic membrane cross-sectional area (EEM) and lumen cross-sectional area (LA) were measured. Plaque area (PA) was calculated as EEM minus LA. Differences between pre- and post-LA (deltaLA), EEM (deltaEEM) and PA (deltaPA) were calculated. RESULTS: Pre-interventional PA (diabetic patients: 12.4 +/- 4.4 mm2 compared with non-diabetic patients: 10.7 +/- 3.6 mm2, = 0.04) and pre-interventional EEM (15.5 +/- 4.4 mm2 compared with 13.6 +/- 3.7 mm2 respectively, P = 0.02) were larger in the diabetic group. Postinterventional PA (10.2 +/- 3.2 mm2 compared with 8.0 +/- 3.4 mm2, P = 0.004) was also larger and postinterventional LA (6.3 +/- 2.2 mm2 compared with 7.4 +/- 2.4 mm2 = 0.04), deltaEEM (0.9 +/- 1.8 mm2 compared with 1.8 +/- 1.8 mm2 P = 0.04) and deltaLA (3.1 +/- 1.6 mm2 compared with 4.2 +/- 2.2 mm2, P = 0.03) were smaller in the diabetic group. The diabetic group exhibited longer lesion lengths (P = 0.04) and a higher inflation pressure was used during revascularization in this patient cohort (P = 0.02). CONCLUSION: Diabetic patients have less reduction of PA during revascularization and because the vessel wall cannot be stretched outwards despite higher inflation pressure, postinterventional LA remains smaller than in the non-diabetic population cohort. This might be a rudiment for consideration of different treatment strategies such as cutting balloon or atherectomy prior to stenting in this population group in order to achieve better procedural outcome.

Effects of radial stretch on target lesion revascularization after percutaneous coronary intervention: an intravascular ultrasound study.

OBJECTIVE: To analyze possible associations between radial stretch during coronary angioplasty and the incidence of target lesion revascularization (TLR). PATIENTS AND METHODS: Intravascular ultrasound images were obtained before and after revascularization in 182 native coronary lesions. The quantitative intravascular ultrasound parameters (external elastic membrane cross-sectional area [EEM-A], lumen areas [LA], plaque area [PA], calculated as EEM-A-LA, and changes between pre- and postinterventional LA [DLA], EEM-A [DEEM-A] and PA [DPA]) were correlated with the incidence of TLR. RESULTS: TLR was performed in 60 (33%) patients, while 122 (67%) patients remained event free. Postinterventional PA remained significantly larger in the TLR group than in the event-free group (9.2 +/- 3.3 mm2 versus 7.9 +/- 3.3 mm2; P=0.02). The radial stretch during intervention, expressed as DEEM-A, and the balloon to artery ratio was significantly larger in the TLR group (DEEM-A: 1.9 +/- 2.1 mm2 versus 1.3 +/- 2.0 mm2; P=0.03; balloon to artery ratio: 1.3 +/- 0.2 versus 1.0 +/- 0.5; P=0.04). Multivariate analysis revealed DEEM-A (P=0.01), DPA (P=0.03), diabetes (P=0.001, odds ratio 5.2, 95% CI 4.9 to 6.5) and adaptive remodelling (P<0.001, odds ratio 4.1, 95% CI 3.5 to 6.4) as independent predictors for TLR. CONCLUSION: Whereas patients in whom lumen gain is achieved primarily by plaque reduction with less wall stretch tend to remain event free, patients with significant radial stretch (ie, less reduction of the PA, but a radial outward shift of the plaque mass) experience a higher incidence of TLR.

Case-based distance measurements for the selection of controls in case-matched studies: application in coronary interventions.

In case-based studies, controls are retrospectively assigned to patients in order to permit a statistical evaluation of the study results through a comparison of the main outcome measures for the patient and retrieved control groups. Inappropriate selection of the controls by using false retrieval parameters or a false algorithm might lead to an incorrect data analysis and a false interpretation of the results. The main hypothesis of the presented study was that, if the matching baseline parameters were at least nearly perfectly selected, then the outcomes of the matched pairs should be similar, or no significant differences in study outcome should be observed between the patients and the matched controls. In the present study, the case-based domain was created from 1566 patients who had undergone intracoronary stent implantation. Uni- and multivariate logistic regression analysis determined nine significant predictors (matching variables) for the occurrence of major adverse cardiac events. An additional 425 consecutive patients undergoing intracoronary stent implantation were then matched with all the potential controls from the database by calculating the individual distance between the patient and the matched control on the basis of the elaborated retrieval algorithm. To test the matching hypothesis, different distance measurements, and an altered outcome and retrieval process were examined. With "flexible" distance measurements, the mean distance between the patients and the first matched controls was 1.31. The major adverse cardiac events were compared in the patient and matched control groups. The best sensitivity and specificity values of the matching system could be achieved in matched pairs with the distance < or =3.00 (95.1% of all patients). On the further stepwise exclusion of the matched pairs exhibiting a distance greater than 2 and 1, then the number of "matchable" controls and the specificity of our matching concept decreased considerably. When the short- or mid-term outcome was compared by using the long-term follow-up matching parameters, no correlation could be found between the treated subjects and controls, indicating that for the other study, main measures of other appropriate parameters must be selected, and demonstrating the importance of the outcome-oriented selection of the retrieval parameters. Furthermore, the outcome measures of the patients and randomly (non-systematically) selected controls did not correlate, revealing the impossibility of drawing correct study conclusions from a non-matched, randomly assigned pairs. In conclusion, the sensitivity and specificity of the matching program, and the study conclusions depend on the appropriately predefined matching parameters and retrieval algorithm.

Adventitial response to intravascular brachytherapy in a rabbit model of restenosis.

BACKGROUND: The incidence of late major adverse cardiac events (MACE) after coronary brachytherapy is higher than in controls. Because expansive remodeling has been shown to correlate with poor clinical outcome after vascular interventions, we studied adventitial changes after intravascular irradiation in a rabbit model. METHODS: Twenty normolipidemic rabbits underwent balloon injury in both external iliac arteries. One artery was assigned for subsequent irradiation with a 90Y source (15 Gy or 30 Gy at 0.5 mm in the vessel wall). After four weeks morphometric measurements were made and cell density and collagen amount determined. Staining for Ki67 identified proliferating cells; apoptotic cells were identified by TUNEL staining. Proliferative and apoptotic indices were calculated as the number of respective positive cells/total cell count x100. RESULTS: The neointimal area decreased to 0.27 +/- 0.3 mm2 after irradiation compared with 0.55 +/- 0.2 mm2 in controls (p=0.007), whereas adventitial area increased from 0.62 +/- 0.3 mm2 to 0.87 +/- 0.3 mm2 (p=0.02). Irradiation reduced both the proliferative (0.95 +/- 2.6 vs. 3.73 +/- 4.7, p=0.026) and apoptotic (0.006 +/- 0.02 vs. 0.107 +/- 0.2, p=0.03) indices in the neointima, but not in the other arterial-wall layers. Collagen amount and arterial remodeling did not differ between the groups. There was no difference between 15 and 30 Gy in any of the parameters, although adventitial thickening was more pronounced in the high-dose group. CONCLUSIONS: In normolipidemic rabbits, intravascular beta-irradiation after balloon angioplasty is associated with an increase in neoadventitia and a reduction of neointima. It is conceivable that this phenomenon may contribute to the increased incidence of late MACE after vascular brachytherapy.

Estimation of doses to personnel and patients during endovascular brachytherapy applications.

In the last few years coronary endovascular brachytherapy using gamma- and beta-emitting radionuclides has been established as a standard treatment procedure to prevent restenosis after percutaneous coronary interventions. Direct measurements and calculations were made to determine personnel doses and organ doses of patients due to gamma rays of 192Ir and beta rays of 90Sr/90Y and 32P sources. In general, our results show that the dose levels are low compared with the X-ray exposure from angiography. The dose rate from bremsstrahlung at 1 m distance from a device containing a 90Sr/90Y source of 2.3 GBq is 4 micro Sv h(-1). The skin dose from beta rays during source transfer into and from the patient was estimated with the directional dose equivalent H'(0.07) of 10 micro Sv at 1 m distance from the catheter. By maintaining safe distances, the dose levels can be kept well within annual dose limits.

Cardiac magnetic resonance postcontrast T1 time is associated with outcome in patients with heart failure and preserved ejection fraction.

BACKGROUND: The underlying pathophysiology of heart failure with preserved ejection fraction (HFPEF) is incompletely understood, but myocardial extracellular matrix accumulation is thought to play a major role. Our aims were to estimate myocardial extracellular matrix using cardiac magnetic resonance T1 mapping and to assess the relationship between pathobiology/pathophysiology and prognosis. METHODS AND RESULTS: Patients with suspected HFPEF (n=100) were enrolled in this prospective, observational study. Confirmatory diagnostic tests, cardiac magnetic resonance imaging including T1 mapping, and invasive hemodynamic assessments were performed at baseline. Sixty-one patients with confirmed HFPEF entered a longitudinal outcome-monitoring phase (mean, 22.9±5.0 months), during which 16 had a cardiac event. Cardiac magnetic resonance T1 time (hazard ratio, 0.99; 95% confidence interval, 0.98-0.99; P=0.046), left atrial area (hazard ratio, 1.08; 95% confidence interval, 1.03-1.13; P<0.01), and pulmonary vascular resistance (hazard ratio, 1.01; 95% confidence interval, 1.00-1.01; P=0.03) were significantly associated with cardiac events. Patients with T1 times below the median (<388.3 ms) were at greater risk of cardiac events than the rest of the group (P<0.01). Extracellular matrix of left ventricular biopsies (n=9), quantified by TissueFAXS technology correlated with T1 time (R=0.98; P<0.01). T1 time also correlated with right ventricular-pulmonary arterial coupling (pulmonary vascular resistance: R=-0.36; P<0.01; right ventricular ejection fraction: R=0.28; P=0.01). CONCLUSIONS: In the present preliminary study, cardiac magnetic resonance postcontrast T1 time is associated with prognosis in HFPEF, suggesting postcontrast T1 as possible biomarker for HFPEF.

Non-invasive algorithms for the diagnosis of pulmonary hypertension.

Precapillary pulmonary hypertension (PH) is diagnosed when mean pulmonary arterial pressure (mPAP) equals or exceeds 25 mmHg and the pulmonary capillary wedge pressure (PCWP) is equal or lower than 15 mmHg. Because both parameters can only be derived from invasive hemodynamic assessment, right heart catheter (RHC) is still a gold standard for the diagnosis of PH. Severe precapillary PH corresponds to pulmonary vascular disease and carries a poor prognosis. Unfortunately, due to a generally low specificity of non-invasive estimates of systolic pulmonary pressure, at least 50% of patients with suspicion of PH need to undergo invasive RHC for exclusion of precapillary PH. Therefore, and also in order to manage the growing number of postcapillary PH due to heart and lung disease in the general population, pulmonary and cardiologic diagnostic algorithms combining multiple parameters have been developed. Recent disease scores are reviewed, and an outlook is given on emerging evidence from the DETECT clinical study holding the promise to non-invasively predict precapillary PH in vulnerable patients. These diagnostic trees help limit unnecessary procedures and help differentiate the current categories of PH. However, one has to keep in mind that the diagnosis of PH is still made by hemodynamic assessment.

Novel c.367_369del LMNA mutation manifesting as severe arrhythmias, dilated cardiomyopathy, and myopathy.

OBJECTIVE: The 3-bp deletion in exon 2 of the Lamin A/C (LMNA) gene has not been described in association with dilated cardiomyopathy, which is characterized by progressive heart failure, atrioventricular (AV) block, tachyarrhythmias, and variable skeletal muscle involvement. CASE REPORT: In a 43-year-old woman with a long-term history of palpitations and newly diagnosed AV blocks I and II, ventricular ectopic beats, inducible nonsustained ventricular tachycardias (VTs), cardiac arrest, and successful resuscitation, an implantable cardioverter defibrillator was successfully implanted. Her family history was positive for sudden cardiac death (her father and sister), dyspnea and heart failure (her grandmother and sister), palpitations (her brother), and elevated levels of creatine-kinase (CK) (her sister). Two cousins had died of nonspecific muscular dystrophy at ages 10 years and 11 years. Upon neurological investigations revealing sore neck muscles, reduced tendon reflexes, and detached, spot-like white matter lesions bilaterally, a neuromuscular disorder was suspected. The direct sequencing of all exons and flanking intronic regions of the LMNA gene detected the heterozygote 3-bp deletion (AAG) c.367_369del in exon 2 of the gene. This mutation resulted in the deletion of a lysine at position 123 (p.lys123del) in the lamin A/C protein. CONCLUSIONS: The novel 3-bp deletion in exon 2 of the LMNA gene may phenotypically manifest as dilated cardiomyopathy, heart failure, severe tachyarrhythmias, and muscular dystrophy. Sudden cardiac death from ventricular fibrillation may be prevented in LMNA mutation carriers if the diagnosis is established early enough to implant a cardioverter defibrillator.