Thriveni Sanagala

Left atrial mechanical responses to right ventricular pacing in heart failure patients: implications for atrial fibrillation.

Left Atrial Function During Right Ventricular Pacing. Background: RV pacing (RVP), even with preserved atrioventricular (AV) synchrony, may lead to left atrial (LA) enlargement and atrial fibrillation. However, inciting events are unknown. We hypothesized that RVP acutely impairs LA function by mechanisms affecting atrial contraction and/or ventricular diastole. Methods: LA function in ICD patients (n = 31, LVEF ≤ 40%) and controls (n = 14, LVEF > 50%) was contrasted between intrinsic conduction versus RVP during asynchronous (ICD, n = 17, control, n = 7), and synchronous (ICD, n = 14, control, n = 14) pacing at long (LAVd, 107 ±16 ms) and short (SAVd, 31 ± 5 ms) AV delays. LA maximal volume (LAMax), minimal volume (LAMin), and emptying fraction {LAEmF = (LAMax–LAMin)/LAMax} were measured echocardiographically. Six‐segment mean mitral annular tissue doppler E′ (global E′) assessed diastolic recoil during baseline and LAVd. Results: In the ICD group, LAMin increased by 42% (P < 0.0009) during VVI, by 31% (P = 0.0002) during SAVd, and by 17% (P < 0.0007) during LAVd. LAEmF decreased by 44% (P < 0.0008), 27% (P < 0.0001), and by 15% (P = 0.003) during VVI, SAVd, and LAVd respectively. LAMax was unaltered. Global E′ was reduced by 12%. In control, LAMin increased and LAEmF decreased significantly during VVI (82 and 58%) and SAVd (46 and 41%), but not during LAVd. Conclusion: In patients with LV dysfunction, RVP acutely impaired LA emptying, and increased minimal volume, most prominently when atrial contraction was impeded (VVI, DDD‐SAVd) but also when completed (DDD‐LAVd), indicating impaired diastolic recoil as an important mechanism. When LV function was normal, similar changes were present when atrial filling is impeded (VVI, SAVd), but not when completed (LAVd). (J Cardiovasc Electrophysiol, Vol. 22, pp. 866‐874, August 2011)

Congenital Sick Sinus Syndrome With Atrial Inexcitability and Coronary Sinus Flutter

Case A 37-year-old asymptomatic male physician from Mexico without any previous medical problems was referred after routine physical examination for evaluation of atrial fibrillation with a slow ventricular rate. Arrhythmia duration was unknown. He stated that bradycardia had been consistently noted on previous clinical examinations and had been attributed to competitive long-distance running since childhood. Heart rates in the “40s” had been noted since age 10 to 11 years when he had been informed of a “heart murmur.” Subsequent echocardiographic examination had been normal. The patient denied any family history of sudden death or arrhythmias. He had no siblings and no children. His prior records (and those of his parents) were unavailable. Physical examination was normal except for a regular bradycardia of 45 beats/min. Twelve-lead ECG showed fixed R-R intervals. No clear P-wave activity was identified. However, there was small-amplitude baseline electric activity of debatable origin, interpreted variously by experienced electrocardiographers as standstill, artifact, or atrial fibrillation waves (Figure 1A). A transthoracic echocardiogram showed normal ventricular volume and function (left ventricular end-diastolic diameter, 52 mm; left ventricle end-systolic diameter, 34 mm) and mild tricuspid regurgitation with estimated pulmonary artery systolic pressure of 40 mm Hg. Both atria were severely enlarged (left atrial volume index, 58 mL; right atrial area, 41 cm). Doppler echocardiographic examination of both tricuspid and mitral atrioventricular (AV) inflow showed complete absence of A waves, indicating lack of left and right atrial contractile activity (Figure 2). A transesophageal echocardiogram did not reveal any evidence of an intracardiac shunt. A Bruce protocol exercise treadmill test was stopped at 10 minutes and 26 s because of patient shortness of breath. Heart rate accelerated gradually to a maximum of 131 beats/min and always remained regular. Baseline atrial activity (if any) was not interpretable because of exercise artifact. Isolated premature ventricular contractions were observed during exercise. A 24-hour Holter monitor showed regular rhythm (mean heart rate, 47 beats/ min; range, 35–95 beats/min; maximum R-R interval, 1.8 s) with 56 ventricular bigeminal cycles. The only symptom during recording periods was an abnormal lateral chest sensation that corresponded with heart rates between 30 and 40 beats/min. The patient underwent an external cardioversion without appreciable change in heart rate (44 beats/min), although electrocardiographic intervals between QRS-T complexes became completely isoelectric for several minutes before small-amplitude deflections resumed (Figure 1B). At electrophysiology study, the first electrode catheter was placed in the CS and demonstrated regular, rapid atrial activity at a cycle length of 274 ms, suggestive of atrial flutter (Figure 3A). In striking contrast, a subsequently placed duodecapolar electrode catheter sited conventionally to map the right atrial free wall and cavotricuspid annulus recorded no electric activity, despite excellent tissue contact. This remained unchanged by deflecting the catheter around the right atrium to include posterior locations or by varying its vertical tilt. Point-by-point electroanatomical mapping (CARTO) confirmed absolute lack of recordable electrograms in the free wall (Figure 4A through 4C). Low-voltage activity was observed in the septum at and above the ostium of the CS. Normal CS electrograms were recorded in the body of the CS but diminished distally. Exploration of the anticipated region of the sinus node (filter settings, 0.05–500 Hz) revealed slow ( 30 beats/min) electric activity in a discrete location without corresponding local atrial depolarization (Figure 4D). Atrial flutter was mapped to a region of the proximal CS and its roof. Fractionated local electrograms were recorded at its junction with the inferior midseptum. Flutter was not pace terminable. Radiofrequency energy applied to the proximal CS slowed tachycardia and rendered it pace terminable. On termination, the His bundle escape rhythm was clear (Figure 3C). The His-ventricular interval (50 ms) was normal. An irregular, dissociated slow atrial escape emerged from the distal CS. No AV or VA conduction was observed with CS or

Association of Cardiomyopathy With MYBPC3 D389V and MYBPC3Δ25bpIntronic Deletion in South Asian Descendants

Importance The genetic variant MYBPC3&Dgr;25bp occurs in 4% of South Asian descendants, with an estimated 100 million carriers worldwide. MYBPC3 &Dgr;25bp has been linked to cardiomyopathy and heart failure. However, the high prevalence of MYBPC3&Dgr;25bp suggests that other stressors act in concert with MYBPC3&Dgr;25bp. Objective To determine whether there are additional genetic factors that contribute to the cardiomyopathic expression of MYBPC3&Dgr;25bp. Design, Setting, andParticipants South Asian individuals living in the United States were screened for MYBPC3&Dgr;25bp, and a subgroup was clinically evaluated using electrocardiograms and echocardiograms at Loyola University, Chicago, Illinois, between January 2015 and July 2016. Main Outcomes and Measures Next-generation sequencing of 174 cardiovascular disease genes was applied to identify additional modifying gene mutations and correlate genotype-phenotype parameters. Cardiomyocytes derived from human-induced pluripotent stem cells were established and examined to assess the role of MYBPC3&Dgr;25bp. Results In this genotype-phenotype study, individuals of South Asian descent living in the United States from both sexes (36.23% female) with a mean population age of 48.92 years (range, 18-84 years) were recruited. Genetic screening of 2401 US South Asian individuals found an MYBPC3&Dgr;25bp carrier frequency of 6%. A higher frequency of missense TTN variation was found in MYBPC3&Dgr;25bp carriers compared with noncarriers, identifying distinct genetic backgrounds within the MYBPC3&Dgr;25bp carrier group. Strikingly, 9.6% of MYBPC3&Dgr;25bp carriers also had a novel MYBPC3 variant, D389V. Family studies documented D389V was in tandem on the same allele as MYBPC3&Dgr;25bp, and D389V was only seen in the presence of MYBPC3&Dgr;25bp. In contrast to MYBPC3&Dgr;25bp, MYBPC3&Dgr;25bp/D389V was associated with hyperdynamic left ventricular performance (mean [SEM] left ventricular ejection fraction, 66.7 [0.7%]; left ventricular fractional shortening, 36.6 [0.6%]; P < .03) and stem cell–derived cardiomyocytes exhibited cellular hypertrophy with abnormal Ca2+ transients. Conclusions and Relevance MYBPC3&Dgr;25bp/D389V is associated with hyperdynamic features, which are an early finding in hypertrophic cardiomyopathy and thought to reflect an unfavorable energetic state. These findings support that a subset of MYBPC3&Dgr;25bp carriers, those with D389V, account for the increased risk attributed to MYBPC3&Dgr;25bp.

High-Throughput Diagnostic Assay for a Highly Prevalent Cardiomyopathy-Associated MYBPC3 Variant

A 25-basepair deletion variant of MYBPC3 occurs at high frequency in individuals of South Asian descent and is estimated to affect 55 million people worldwide, carrying an increased likelihood of cardiomyopathy. Since this variant is prevalent and severe in this subpopulation, quick and affordable screening to provide risk-assessment to guide treatment for these patients is critical. An RNaseH qPCR assay was developed to quickly and specifically diagnose the presence of the 25-basepair deletion variant in MYBPC3. RNAseH-blocked nucleotide primers were designed to identify the presence or absence of the wild type MYBPC3 allele or the genomic sequence containing the 25-basepair deletion. Using this assay, three blinded operators were able to accurately determine the genotype from human genomic DNA samples from blood and saliva using a qPCR thermocycler. Furthermore, positive variant subjects were examined by both electrocardiography and echocardiography for the presence of cardiomyopathy. A simple, robust assay was established, verified and validated that can be automated to detect the presence of the highly prevalent 25-basepair deletion MYBPC3 variant using both blood and saliva samples. The assay will provide quick and accurate prescreening of individuals at high risk for cardiomyopathies and allow for better clinical identification of 25-basepair deletion MYBPC3 carriers in large cohort epidemiological studies.

Left ventricular noncompaction as diagnosed by established cardiac magnetic resonance imaging criteria is not associated with increased adverse events compared to non-ischemic dilated cardiomyopathy

Background Left ventricular noncompaction (LVNC) is classified by the American Heart Association as a primary genetic cardiomyopathy and is attributed to defects in cardiac embryogenesis resulting in the intrauterine arrest of the compaction of the loose meshwork that makes up the fetal myocardium. From echocardiographic data, the prevalence of LVNC has been estimated at 0.05% of the general population. With the increasing use of cardiac magnetic resonance imaging (CMR), there has been a surge in the reports of patients with LVNC. Interestingly, many patients that have been diagnosed with non-ischemic dilated cardiomyopathy (NIDCM) have also been noted to have prominent left ventricular trabeculations. We sought to evaluate the difference in clinical outcomes in patients with NIDCM compared to those with LVNC as diagnosed by established CMR criteria.

Comparison of two methods of right atrial volume assessment using cardiac magnetic resonance imaging: area-length method versus multislice volumetric method

Background Right atrial (RA) volume evaluation is not as well characterized as left atrial (LA) volume assessment. RA volumes are most accurately assessed by the multislice volumetric (MSV) method; however, this method is time consuming requiring manual tracing of RA endocardial borders over several slices. The area-length (AL) method can also be used to estimate RA volume. Although well established for the assessment of LA size, the application of the AL method to the RA is not as well established. We sought to determine the accuracy, limits of agreement, inter-observer, and intra-observer variability of the AL method compared to the MSV method on the measurement of RA volume. Methods We prospectively studied 67 patients who underwent cardiac magnetic resonance imaging (CMR) for a clinically indicated reason. CMR images were acquired on 3 Tesla (Siemens Trio) or 1.5 Tesla (Siemens Aera) scanner using cine steady-state free precession (SSFP) sequence. RA volumes using MSV method were measured from a stack of long-axis slices acquired parallel to the left ventricular 2 chamber plane, which spanned the entire RA and right ventricle (RV). RA volumes using the AL method were measured from a 4-chamber and 2-chamber view of the RA and RV. The RA appendage was included in the RA volumes. RA volumes calculated by MSV and AL methods were compared using Pearson’s correlation, regression analysis and Bland-Altman analysis. Inter-observer and intra-observer variability was assessed on a random sample of 10 patients and analyzed by intra-class correlation coefficients and Bland-Altman analysis. Results Mean indexed RA volumes (RAVI) by AL method did not differ significantly when compared with the MSV method (63.7 ± 26.2 vs 62.1 ± 22.7 ml/m 2 ,p=0 .29). The AL method correlated highly with MSV method (r = 0.86); however, Bland-Altman analysis demonstrated wide limits of agreement (mean difference 1.7 ± 13.4 ml/m 2 ). Intraobserver analysis revealed excellent agreement for both

Left atrial volume assessment by area-length method compared to multislice volumetric method using cardiovascular magnetic resonance imaging

Background Left atrial (LA) size is a strong predictor of cardiovascular events in patients with atrial fibrillation (AF) and a variety of other cardiovascular diseases. Left atrial volume (LAV) measurement is the preferred method for assessment of LA size. The most widely used technique for LAV assessment is the area-length (AL) method using 2D echocardiography. Studies have shown that AL method by echocardiography significantly underestimates LAV when compared with CMR using multislice volumetric (MSV) method. However, MSV method is time consuming due to increased acquisition and analysis time. We sought to compare LAV assessment by CMR using the more rapid AL method with MSV method. Methods We prospectively studied 273 patients with AF who underwent CMR on a 3T scanner (Siemens Trio). Image acquisition included SSFP cine of LA in short axis-stack, horizontal long-axis (4 chamber) and vertical long-axis (2 chamber) views. LAV by AL method was measured on CMR long axis views in end-systole as recommended by the American Society of Echocardiography. LAV by MSV method was performed by tracing the LA endocardial border on LA short axis stack in a phase with largest LA dimension. LA appendage and pulmonary veins were excluded by both methods. LAV and LAV index measurements by AL and MSV methods were compared using Pearson’s correlation, Regression analysis and Bland-Altman plots. Results CMR was successfully completed and analyzed in 252 patients; mean age 60.5 ± 10.7 years, 185 males (73.4%). Paroxysmal AF was the most common arrhythmia (57.5%). Mean CHA2DS2-VASc score was 1.7 ± 1.3. Coronary artery disease was present in 31 (12.3%), hypertension 154 (61.1%), heart failure 7 (2.8%), diabetes mellitus 34 (13.5%), TIA/CVA 18 (7.1%) and peripheral vascular disease in 7 (2.8%) patients. Mean heart rate during CMR was 68.7 ± 15.6 beats/ min, 82% were in sinus rhythm. Mean left ventricular EF was 58.6 ± 8.1% and right ventricular EF was 47 ± 7.2%. Table 1 shows the mean LAV and LAV index by AL and MSV methods and their correlation. LAV and LAV index by the AL method was significantly higher compared to MSV method (p <0.001 for both). AL method showed good correlation with MSV method. Bland-Altman plot showed mean measurement difference of 5.5 ± 10.5 ml/m 2 for LAV index between two methods. AL method tend to overestimate LAV index compared to MSV method by 26 ml/m 2 or underestimate by 14.9 ml/m 2 (Figure 1). Conclusions LA volume measurements by CMR AL method correlate well with the MSV method but limits of agreement are wide. These differences should be taken into account when using AL method for clinical or research purposes.

Left atrial volume assessment in atrial fibrillation using multimodality imaging: a comparison of echocardiography, invasive three dimensional CARTO and cardiac magnetic resonance imaging

Left atrial size in atrial fibrillation is a strong predictor of successful ablation and cardiovascular events. Cardiac magnetic resonance multislice method (CMR-MSM) is the current gold standard for left atrial volume (LAV) assessment but is time consuming. We investigated whether LAV with more rapid area-length method by echocardiography (Echo-AL) or cardiac magnetic resonance (CMR-AL) and invasive measurement by 3D-CARTO mapping during ablation correlate with the CMR-MSM. We studied 250 consecutive patients prior to atrial fibrillation ablation. CMR images were acquired on 3T scanner to measure LAV by MSM and biplane area-length method. Standard echocardiography views were used to calculate LAV by biplane area-length method. LAV during ablation was measured by 3D-CARTO mapping. LAV was compared using intra-class correlation (ICC), Pearson’s correlation and Bland–Altman plots. CMR-MSM was used as the reference standard. Mean LAV using CMR-MSM was 112.7 ± 36.7 ml. CMR-AL method overestimated LAV by 13.3 ± 21.8 ml (11.2 %, p < 0.005) whereas 3D-CARTO and Echo-AL underestimated LAV by 8.3 ± 22.6 and 24.0 ± 27.6 ml respectively (8.7 % and 20.0 % respectively, p < 0.005). There was no significant difference between paroxysmal and persistent atrial fibrillation. CMR-AL and 3D-CARTO correlated and agreed well with CMR-MSM (r = 0.87 and 0.74, ICC = 0.80 and 0.77 respectively). However, Echo-AL had poor correlation and agreement with CMR-MSM (r = 0.66 and ICC = 0.48). Bland–Altman plots confirmed these findings. CMR-AL method may be used as an alternative to CMR-MSM, as it is non-invasive, rapid, and correlates well with CMR-MSM. LAV by different modalities should not be used interchangeably.